Gene:
HLA-B
major histocompatibility complex, class I, B

Available Guidelines

  1. CPIC Dosing Guideline for abacavir and HLA-B
  2. CPIC Dosing Guideline for allopurinol and HLA-B
  3. CPIC Dosing Guideline for carbamazepine and HLA-B
  4. CPIC Dosing Guideline for phenytoin and CYP2C9, HLA-B
  5. Professional Society Guideline for allopurinol and HLA-B
  6. Professional Society Guideline for carbamazepine and HLA-B
  7. Dutch Pharmacogenetics Working Group Guideline for abacavir and HLA-B
  8. Dutch Pharmacogenetics Working Group Guideline for ribavirin and HLA-B

last updated 02/28/2014

CPIC Dosing Guideline for abacavir and HLA-B

Summary

In individuals with the HLA-B*57:01 variant allele ("HLA-B*57:01-positive"), abacavir is not recommended and should be considered only under exceptional circumstances. See full guideline for disclaimers, further details and supporting evidence.

There's more of this guideline. Read more.


last updated 10/17/2012

CPIC Dosing Guideline for allopurinol and HLA-B

Summary

Allopurinol is contraindicated in individuals with the HLA-B*58:01 variant allele ("HLA-B*58:01-positive") due to significantly increased risk of allopurinol-induced SCAR.

There's more of this guideline. Read more.



last updated 08/05/2014

CPIC Dosing Guideline for phenytoin and CYP2C9, HLA-B

Summary

Phenytoin is contraindicated in individuals with the HLA-B*15:02 variant allele ("HLA-B*15:02-positive") due to significantly increased risk of phenytoin-induced cutaneous adverse reactions of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Additionally, patients with the CYP2C9 poor metabolizer phenotype may require reduced doses of phenytoin.

There's more of this guideline. Read more.



last updated 03/11/2014

Professional Society Guideline for carbamazepine and HLA-B

Summary

The Canadian Pharmacogenomics Network for Drug Safety (CPNDS) clinical recommendation group has published guidelines for the use of HLA-B*15:02 genotype when prescribing carbamazepine (CBZ). They recommend that carbamazepine not be prescribed for CBZ-naive patients who carry at least one HLA-B*15:02 allele.

There's more of this guideline. Read more.




PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.



last updated 10/25/2013

FDA Label for abacavir and HLA-B

This label is on the FDA Biomarker List
Genetic testing recommended

Summary

The FDA-approved label for abacavir recommends genetic testing for the HLA-B*5701 allele prior to initiating or reinitiating treatment with abacavir in patients of unknown HLA-B*5701 status, and due to a high risk of hypersensitivity reaction abacavir is not recommended in individuals carrying this allele.

There's more of this label. Read more.


last updated 10/25/2013

FDA Label for carbamazepine and HLA-B

This label is on the FDA Biomarker List
Genetic testing required

Summary

The FDA-approved label for carbamazepine (Tegretol) states that screening of patients with ancestry in genetically at-risk populations (patients of Asian descent) for the presence of the HLA-B*1502 allele should be carried out prior to initiating treatment with Tegretol due to a high risk of serious and sometimes fatal dematologic reactions. Patients positive for the HLA-B*1502 allele should not be treated with Tegretol, unless the benefit clearly outweighs the risk. Association with the HLA-A*3101 and the risk of developing hypersensitivity reactions to carbamazepine is also mentioned in the label, though testing for this allele is not required.

There's more of this label. Read more.


last updated 10/25/2013

FDA Label for phenytoin and HLA-B

This label is on the FDA Biomarker List
Actionable PGx

Summary

A strong association between the risk of developing SJS/TEN and the presence of HLA-B*1502, an inherited allelic variant of the HLA B gene, in patients using carbamazepine. Limited evidence suggests that HLAB*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin. Consideration should be given to avoiding phenytoin as an alternative for carbamazepine in patients positive for HLA-B*1502.

There's more of this label. Read more.


last updated 10/15/2013

European Medicines Agency (EMA) Label for abacavir and HLA-B

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) states screening for the HLA-B*5701 allele should be carried out prior to initiating abacavir treatment and recommends screening in patients of unknown HLA-B*5701 allele status who are reinitiating treatment with abacavir. Due to a high risk of hypersensitivity reaction abacavir is not recommended in individuals carrying this allele.

There's more of this label. Read more.


Clinical Variants that meet the highest level of criteria, manually curated by PharmGKB, are shown below. Please follow the link in the "Position" column for more information about a particular variant. Each link in the "Position" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Related Drugs?
HLA-B*5701 Test rs2395029 , HLA-B HLA-B*5701
HLA-B*5801 Typing (Allopurinol hypersensitivity) HLA-B*58:01:01 , rs9263726
HLA-B*5801 for Allopurinol Induced Stevens-Johnson Syndrome Risk HLA-B*58:01:01 , rs9263726
Identification of drug hypersensitivity related HLA genes, Including HLA-B*5801 with Allopurinol HLA-B*58:01:01 , rs9263726
Pharmigene HLA-B*5801 Detection HLA-B*58:01:01 , rs9263726
HLA-B*1502 Carbamazepine Sensitivity rs3909184 , rs2844682 , HLA-B HLA-B*1502

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No VIP available VA *07:02:01 N/A N/A N/A
No VIP available No VIP available VA *08:01:01 N/A N/A N/A
No VIP available CA VA *13:01:01 N/A N/A N/A
No VIP available CA VA *13:02:01 N/A N/A N/A
No VIP available No VIP available VA *15:01:01:01 N/A N/A N/A
No VIP available CA VA *15:02:01 N/A N/A N/A
No VIP available CA VA *15:19 N/A N/A N/A
No VIP available No VIP available VA *15:10:01 N/A N/A N/A
No VIP available CA VA *15:11:01 N/A N/A N/A
No VIP available CA VA *15:18:01 N/A N/A N/A
No VIP available CA VA *15:27:01 N/A N/A N/A
No VIP available No VIP available VA *18:02 N/A N/A N/A
No VIP available CA VA *27:09 N/A N/A N/A
No VIP available No VIP available VA *27:05:02 N/A N/A N/A
No VIP available CA VA *35:01:01:01 N/A N/A N/A
No VIP available CA VA *35:05:01 N/A N/A N/A
No VIP available No VIP available VA *37:01:01 N/A N/A N/A
No VIP available CA VA *38:01:01 N/A N/A N/A
No VIP available CA VA *38:02:01 N/A N/A N/A
No VIP available No VIP available VA *39:01:01:01 N/A N/A N/A
No VIP available No VIP available VA *40:03 N/A N/A N/A
No VIP available CA VA *40:01:01 N/A N/A N/A
No VIP available No VIP available VA *40:02:01 N/A N/A N/A
No VIP available No VIP available VA *40:06:01:01 N/A N/A N/A
No VIP available No VIP available VA *41:01 N/A N/A N/A
No VIP available CA VA *44:02:01:01 N/A N/A N/A
No VIP available No VIP available VA *44:03:01 N/A N/A N/A
No VIP available No VIP available VA *46:01:01 N/A N/A N/A
No VIP available CA VA *48:01 N/A N/A N/A
No VIP available CA VA *48:04 N/A N/A N/A
No VIP available No VIP available VA *48:01:01 N/A N/A N/A
No VIP available CA VA *51:01:01 N/A N/A N/A
No VIP available No VIP available VA *51:02:01 N/A N/A N/A
No VIP available No VIP available VA *52:01:01:01 N/A N/A N/A
No VIP available No VIP available VA *54:01:01 N/A N/A N/A
No VIP available No VIP available VA *55:01:01 N/A N/A N/A
No VIP available CA VA *56:02 N/A N/A N/A
No VIP available No VIP available VA *56:01:01 N/A N/A N/A
No VIP available CA VA *57:01:01 N/A N/A N/A
No VIP available CA VA *58:01 N/A N/A N/A
No VIP available No VIP available VA *58:02 N/A N/A N/A
No VIP available CA VA *59:01:01:01 N/A N/A N/A
No VIP available No VIP available VA *67:01:01 N/A N/A N/A
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  None
Alternate Symbols:  None
PharmGKB Accession Id: PA35056

Details

Cytogenetic Location: chr6 : p21.33 - p21.33
GP mRNA Boundary: chr6 : 31321649 - 31324989
GP Gene Boundary: chr6 : 31318649 - 31334989
Strand: minus
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

Introduction

The human leukocyte antigen B (HLA-B) gene is a member of the major histocompatibility complex (MHC), a region of the human genome located on chromosome 6. The MHC (also known as the human leukocyte antigen (HLA) complex) includes three subregions, designated as class I, class II and class III. Each of these subregions contains a variety of genes that mainly code for proteins involved in the immune system. HLA-B is part of the class I group, along with HLA-A and HLA-C, all three of which code for their eponymous proteins [Article:15573121]. Class II genes include HLA-DR, HLA-DP and HLA-DQ [Article:22076556], and class III genes include complement components and cytokines such as complement factor B (CFB) and members of the tumor necrosis factor (TNF) family [Articles:15573121, 14656967]. The MHC is a large region of the genome, and contains many other genes besides the ones listed above (please see [Horton et al.][PMID: 15573121] for more details). The HLA genes are important within the field of pharmacogenetics: variations within these genes have been associated with severe drug reactions, as well as changes in how well a patient responds to a drug.

The HLA-B protein and the other class I group members are cell-surface molecules responsible for the presentation of endogenous peptides to CD8+ T-cells, and exist on almost all nucleated cells. This is in contrast to class II molecules, which display exogenous peptides to CD4+ T-cells, and are present only on antigen presenting cells (APCs) such as macrophages or dendritic cells [Articles:22076556, 18641646]. This presentation of peptides to T-cells assists in the recognition of pathogens [Article:22076556]. As a class I molecule, most of the peptides that HLA-B presents come from the normal breakdown of host cellular proteins, and are recognized by the immune system as such (i.e. "self" peptides). However, when a cell becomes infected by a pathogen, the proteins presented will be from the pathogen and recognized as foreign or "non-self". T cell antigen receptors (TCRs) on CD8+ cytotoxic T cells are responsible for this recognition, and will stimulate an immune reaction that destroys the cell [Janeway, Immunobiology, 5th edition].

Class I molecules are expressed in a codominant fashion, and humans inherit a set of HLA-A, B and C genes from each parent. Therefore, given allelic variations within these genes, up to six different class I molecules can be expressed on a cell surface. HLA-A, B and C are heterodimers consisting of an α chain, encoded by their respective genes, and a protein known as β2-microglobulin, which is encoded on chromosome 15. The α chain of HLA-B has four domains: one cytoplasmic, one transmembrane, one which binds to CD8+ cytotoxic T cells, and one which makes up a peptide-binding groove, where the presented peptide is nestled [Janeway, Immunobiology, 5th edition]. This peptide-binding region of the gene is highly polymorphic, and allelic differences between class I genes are often due to variations within this region [Article:22076556][Janeway, Immunobiology, 5th edition]. Indeed, allelic variants of class I genes can differ from one another by up to 20 amino acids. Peptides bind to the groove through interaction with specific amino acid residues, so any amino acid changes due to allelic variation may affect the peptide-binding specificity of a class I molecule [Janeway, Immunobiology, 5th edition] (class II molecules have more flexibility in peptide-binding; see Janeway). The type of extensive polymorphism seen in HLA genes allows a wide variety of peptides to be presented, and likely evolved in order to effectively combat pathogens [Janeway, Immunobiology, 5th edition]. In addition to affecting the peptides capable of being presented, allelic variants in the HLA-B gene have also been associated with susceptibility and resistance to numerous diseases, as well as adverse reactions to a wide range of pharmaceuticals. This makes HLA-B highly relevant to pharmacogenetic research.

HLA-B allele frequencies and nomenclature

Due to the highly polymorphic nature of class I genes, a large number of HLA-B alleles have been identified. Information on the frequencies of over 2800 HLA-B alleles in populations worldwide can be found at The Allele Frequency Net Database; allele frequencies for specific polymorphisms will be discussed within the individual HLA-B allele summaries. Systematic nomenclature for these alleles is invaluable given their quantity. The HLA nomenclature committee has provided a detailed nomenclature to this end, and comprehensive information on the allele naming process can be found at their website. Briefly, all HLA alleles receive at least a four-digit name, consisting of two sets of two digits separated by a colon. Longer names can be assigned if more detail is necessary, such as type or location of nucleotide substitution (e.g. synonymous or intronic) or resultant protein expression (e.g. null protein or cytoplasmic protein). The first set of digits before the colon describes the type, typically the antigen designation used to describe the HLA alleles prior to genetic sequencing. Since these antigen groups commonly have a genetic and biological basis, they have remained in the current HLA nomenclature. The second set of digits indicates the specific allele, numerically ordered based on when the DNA sequence was discovered. This set of digits describes nonsynonymous substitutions only. As an example, in the case of HLA-B*57:01, B*57 is a group of alleles which encode the B*57 antigen or have sequence homology to other B*57 alleles; 01 indicates the specific allele, and its associated nucleotide substitutions which result in amino acid changes. If a nucleotide change does not result in an amino acid change, this can be indicated in a third set of digits [Articles:21071412, 22378157]. This VIP summary will only refer to the first one or two sets of digits. For more detailed information on the naming process, please refer to the HLA nomenclature website.

HLA-B and disease associations

A number of HLA-B alleles or allele groups have been associated with susceptibility or resistance to particular diseases. These include HLA-B*53 and resistance to malaria [Articles:1280333, 1865923], HLA-B*51 and susceptibility to the inflammatory condition Beçhet's disease [Articles:20622878, 11053265], and HLA-B*46 and increased risk of Graves' disease, an autoimmune disorder [Article:23329888]. Two particularly strong disease associations are HLA-B*57 and HIV long-term non-progression, and HLA-B*27 and ankylosing spondylitis.

HLA-B*57 and HIV long-term non-progression

Without treatment, almost all people infected with HIV will ultimately progress to acquired immunodeficiency syndrome (AIDS). However, a small percentage of patients do not advance, even long after the median progression time. These patients are referred to as long-term non-progressors or "elite controllers", and HLA-B*57 alleles, particularly *57:01 and *57:03, are highly enriched in this group of individuals [Articles:20445539, 14685052, 10694578, 21106806, 22718199, 22090105, 20205591, 23365442]. Though this association is well known, the mechanism by which it occurs remains unclear. Kosmrlj et al. used computer algorithms to predict that less than half the number of unique peptides (derived from the human proteome) bound to the HLA-B*57:01 protein as compared to HLA-B*07:01 (a non-HIV-protective form of the molecule). The authors suggested that this affected repertoire development, leading to T-cells that had been exposed to fewer self-peptides. This in turn may lead to a higher frequency of T-cells that recognize viral peptides, such as those from HIV, as well as T-cells that are more cross-reactive toward mutant epitopes. These qualities would enable the T-cells to better control the HIV infection, keeping the viral load in check and thereby making the development of AIDS unlikely [Article:20445539].

HLA-B*27 and ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease, affecting mainly the axial skeleton and sacroiliac joints. It leads to inflammatory back pain, as well as other clinical features including enthesitis and anterior uveitis [Article:17448825]. Presence of HLA-B*27 leads to the greatest risk for AS, and this form of HLA-B is found in over 90% of AS patients with European ancestry. However, only 1-5% of HLA-B*27 individuals will go on to develop AS, and not all alleles of HLA-B*27 are associated with its development. While HLA-B*27:05, *27:02, *27:04 and *27:07 do confer risk, other types such as *27:06 and *27:09 do not appear to be associated with the disease [Article:16777585]. As with HIV and HLA-B*57:01, the mechanism behind this association is unknown, though several theories have attempted to explain the relationship. These include the "arthritogenic peptide" theory, which suggests that HLA-B*27 binds particular peptides that give rise to a cytotoxic T-cell response [Article:10880047], the homodimer theory, which suggests that HLA-B*27 forms homodimers that accumulate and lead to an inflammatory stress response [Articles:12616495, 16777585], and the Klebsiella theory, where the bacteria acts as a trigger for the development of AS [Article:16941202].

HLA-B Testing

Several options exist for determining whether a patient carries a particular HLA-B allele. The first is by direct sequencing of the gene, and assignment of a star allele after checking the sequence against known HLA-B alleles. Another commonly used approach is genotyping, where the sequence variants known to define a particular HLA-B allele are detected using polymerase chain reaction (PCR) primers specific for each variant. It is also possible to test for the presence of an HLA-B allele by genotyping for one more more single nucleotide polymorphirms (SNPs) nearby and in linkage disequilibrium with that allele. However, linkage disequilibrium can vary across populations, and this method may have lower accuracy [Articles:22378157, 23695185]. It is important to note that currently, the high level of polymorphism within the HLA genes makes HLA genotyping at a high resolution challenging [Articles:22651253, 23302098, 23714642]. Present sequencing methods can result in ambiguous typing results with an inability to resolve phase [Articles:22651253, 23302098]. Additionally, different alleles may share similar sequences within the sequenced region [Article:23714642], and defining polymorphisms may lie outside the amplified region [Articles:22651253, 23302098]. These issues may be resolved through next-generation sequencing (NGS), which allows for clonal amplification and massively parallel sequencing. These two properties provide phase information and the ability to sequence more and larger regions of genes, including intronic regions [Articles:22651253, 23302098].

A list of commercially available genetic tests for various HLA-B alleles can be found on PharmGKB; a more comprehensive list can be found at the Genetic Testing Registry. Since HLA-B expression is co-dominant, HLA-B genotyping results are either "positive", with *57:01 being present in one or both copies of the gene, or "negative", where no copies of the allele are present; there is no intermediate phenotype [Article:22378157].

HLA-B pharmacogenetics

HLA-B alleles have been associated with reactions to a large number of different drugs. Some of these associations have been well studied, such as HLA-B*57:01 and abacavir hypersensitivity, HLA-B*58:01 and allopurinol-induced severe cutaneous adverse reactions (SCARs), and HLA-B*15:02 and carbamazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). Other associations that are not as widely studied, but still show significant results include HLA-B*57:01 and flucloxacillin-induced liver injury, HLA-B*15:02 and phenytoin-induced SJS and TEN (SJS/TEN), HLA-B*35:05 and nevirapine-induced skin rash, and HLA-B*44 and responsiveness to ribavirin. A list of various HLA-B alleles and their pharmacogenetic associations (along with their positive and negative predictive values, if available) can be seen in Table 1 below.

Table 1: List of HLA-B alleles and their associated drug phenotypes. The phenotypes listed for each drug are more likely to occur in patients who are carriers for the associated allele. For example, carriers of *57:01 who are given abacavir have an increased chance of a hypersensitivity reaction as compared to non-carriers. When available, positive and negative predictive values are also shown. Click on the risk allele links to read more information about the pharmacogenetics of that particular allele.
HLA-B risk allele Drug Associated Phenotype References PPV NPV Reference
*57:01 Abacavir Hypersensitivity reaction Refer to table on the allele page 47.9% 100% [Article:18256392]
*57:01 Flucloxacillin Drug-induced liver injury [Article:19483685]
*58:01 Allopurinol SCARs, MPE Refer to table on the allele page 1.5% 100% [Article:19696695]
*15:02 Carbamazepine SJS/TEN Refer to table 1 on the allele page 1.8% 100% [Article:23132554]
*15:02 Phenytoin SJS/TEN Refer to table 2 on the allele page 33% 100% [Article:18637831]
*35:05 Nevirapine Skin rash [Article:19104471]
*44 Ribavirin Sustained response [Article:12873589]

PPV, positive predictive value; NPV, negative predictive value; SCARs, severe cutaneous adverse reactions; MPE, maculopapular eruption; SJS/TEN, Stevens-Johnson Syndrome/toxic epidermal necrolysis

Many other HLA-B alleles besides the ones mentioned above have shown associations with various drug phenotypes. A table of these alleles and their study results can be found in Table 2 below; this table is updated as new findings come to our attention. Since there is no difference in phenotype depending on whether one or two HLA-B alleles are present, most pharmacogenetic studies only consider whether an individual has the allele or not. Therefore, in this table,
"prevalence" of an HLA-B allele refers to how many patients carry that allele, and not the frequency of the allele in the population. Some studies do use allele frequencies in their statistical analyses, and these cases are noted within the table (footnote 1).

Table 2: List of additional HLA-B alleles and their associated drug phenotypes. The phenotypes listed for each drug are more likely to occur in patients who are carriers for the associated allele. For example, carriers of *13:01 who are exposed to trichloroethylene have an increased chance of hypersensitivity dermatitis as compared to non-carriers.
HLA-B allele Drug Reference Phenotype Population Allele prevalence p-value Odds ratio (95% CI)
*13:01 Trichloroethylene
[Article:18007983] HSD Chinese Case: 83/113 (73.5%)
Tolerant controls: 13/142 (9.2%) 1.5 x 10 -21 27.5 (13.5 - 55.7)
*13:02 Oxcarbazepine
[Article:22818943] MPE Han Chinese Case: 4/28 1 (14.3%)
Population control: 11/528 1 (2.1%) 0.001 7.83 (2.32 - 26.41)
Tolerant control: 4/70 1 (5.7%) 0.32 2.75 (0.64 - 11.87)
*15:02 Oxcarbazepine
[Article:21169036] MPE Han Chinese Case: 4/9 (44.4%) 1
Population control: 6/72 1 (8.3%) 0.011 8.8 (1.85 - 41.79)
Tolerant control: 1/9 1 (11.1%) 0.294 6.4 (0.54 - 74.89)
*15:11 Carbamazepine
[Article:21917426] SJS Korean Case: 3/7 (42.9%)
Population control: 19/485 (3.9%) 0.002 18.4 (3.8 - 88)
Tolerant control: 2/50 (0.04%) NS
[Article:22348435] SJS/TEN Han Chinese Case: 2/36 1 (5.6%)
Population controls: 1/528 1 (0.2%) 0.01 31 (2.74 - 350.5)
[Article:21204807] SJS/TEN 2 Japanese Case: 4/28 1 (14.3%)
Population controls: 6/986 1 (0.6%) 0.0004 16.3 (4.76 - 55.6)
*15:18 Carbamazepine
[Article:19694795] SJS Japanese Case: 1/5 (20%)
Population control: 4/493 (0.9%) 13.58 (relative risk)
*15:19 Oxcarbazepine
[Article:22818943] MPE Han Chinese Case: 1/28 1 (3.6%)
Population control: 0/1138 1 (0%) 0.024 124.2 (4.94 - 3118)
Tolerant control: 0/70 1 (0%) 0.29 7.69 (0.3 - 194.59)
*15:27 Oxcarbazepine
[Article:22818943] MPE Han Chinese Case: 2/28 1 (7.1%)
Population control: 1/528 1 (0%) 0.007 40.54 (3.56 - 461.64)
Tolerant control: 0/70 1 (0%) 0.08 13.3 (0.62 - 286.29)
*27:09 Oxcarbazepine
[Article:22818943] MPE Han Chinese Case: 1/28 1 (3.6%)
Population control: 0/1138 1 (0%) 0.024 124.2 (4.94 - 3117.64)
Tolerant control: 0/70 1 (0%) 0.29 7.69 (0.3 - 194.59)
*35:01 Nevirapine
[Article:24911354] HSR White & Asian Case: 6/19 (31.6%)
Tolerant control: 27/261 (10.5%) 0.01 5.1
*38 Peg-IFN / Ribavirin
[Article:23360626] NR Egyptian Case: 10/88 (11.4%)
Control (SVR): 2/112 (1.8%) 0.011 3 7.05 (1.39 - 18.01) 3
*38:02 Oxcarbazepine
[Article:23829937] MPE Han Chinese Case: 3/28 1 (10.7%)
Population control: 23/1236 1 (1.9%) 0.018 6.33 (1.78 - 22.46)
Tolerant control: 2/56 1 (3.6%) 0.42 3.24 (0.51 - 20.63)
*48:01 Allopurinol
[Article:24858023] MPE Korean Case: 3/13 (23.1%)
Population control: 33/485 (6.8%) 0.038 4.11 (1.08 - 15.66)
Tolerant control: 34/440 (7.7%) 0.061 3.58 (0.94 - 9.1)
*48:04 Oxcarbazepine
[Article:22818943] MPE Han Chinese Case: 1/28 1 (3.6%)
Population control: 0/1138 1 (0%) 0.024 124.2 (4.94 - 3117.64)
Tolerant control: 0/70 1 (0%) 0.29 7.69 (0.3 - 194.59)
*51:01 Phenobarbital
[Article:24236482] SJS/TEN Japanese Case: 7/16 1 (43.8%)
Population control: 453/5756 1 (7.9%) 0.0042 16.71 (3.66 - 83.06)
*58:01 Carbamazepine
[Article:24399721] SJS/TEN Han Chinese Case: 4/20 (20.0%)
Tolerant control: 6/125 (4.8%) 0.013 4.96 (1.26 - 19.46)
*59:01 Acetazolamide
[Article:21342230] SJS Korean Case: 1/1 (100%)
*59:01 Carbamazepine
[Article:19694795] SJS Japanese Case: 2/5 (40%)
Population control: 8/493 (1.7%) 15.16 (relative risk)
*59:01 Methazolamide
[Article:20504258] SJS/TEN Korean Case: 5/5 (100%)
Population control: 20/485 (4.1%) < 0.001 249.8 (13.4 - 4813.5)
[Moon et al.] SJS Korean Case: 5/6 (83.3%)
[Sung et al.] SJS/TEN Korean Case: 2/2 (100%)
[Article:9109770] SJS Japanese Case: 3/3 (100%)

Table last updated 08/26/2014

HSD, hypersensitivity dermatitis; MPE, maculopapular eruption; SJS, Stevens-Johnson Syndrome; TEN, toxic epidermal necrolysis; Peg-IFN, peginterferon alfa-2a; HSR, hypersensitivity reaction; NR, non-response; SVR, sustained virological response

1 - Allele frequencies
2 - "Probable" SJS cases included
3 - Also significant in logistic regression (p = 0.009, OR = 7.92 (1.67 - 37.54))

Citation
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
History

Submitted by Julia Barbarino

Haplotype Summaries HLA-B *15:02:01, HLA-B *57:01:01, HLA-B *58:01:01
Drugs
Diseases
Pathways

Haplotype Overview

Source of these HLA allele names: http://hla.alleles.org/ (HLA Informatics Group 1995-2012)

References:

  • [Article:21071412] Robinson J, Mistry K, McWilliam H, Lopez R, Parham P, Marsh SGE: The IMGT/HLA database. Nucleic Acids Research. 2011 39 Suppl 1:D1171-6.
  • [Article:10777106] Robinson J, Malik A, Parham P, Bodmer JG, Marsh SGE: IMGT/HLA - a sequence database for the human major histocompatibility complex. Tissue Antigens. 2000 55:280-7.
  • [Article:20356336] SGE Marsh, ED Albert, WF Bodmer, RE Bontrop, B Dupont, HA Erlich, M Fernández-Vina, DE Geraghty, R Holdsworth, CK Hurley, M Lau, KW Lee, B Mach, WR Mayr, M Maiers, CR Müller, P Parham, EW Petersdorf, T Sasazuki, JL Strominger, A Svejgaard, PI Terasaki, JM Tiercy, J Trowsdale: Nomenclature for factors of the HLA system, 2010. Tissue Antigens 2010 75:291-455.

Source: PharmGKB

All alleles in the download file are on the positive chromosomal strand. PharmGKB considers the first haplotype listed in each table as the reference haplotype for that set.

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

PharmGKB contains no curated pathways for this gene. If you would like to volunteer to work on a pathway, please let us know.

External Pathways

Links to non-PharmGKB pathways.

  1. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell - (Reactome via Pathway Interaction Database)
No related genes are available

Curated Information ?

Evidence Drug Class
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
antiepileptics
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
interferons

Curated Information ?

Publications related to HLA-B: 157

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical Application of Pharmacogenomics: The Example of HLA-Based Drug-Induced Toxicity. Public health genomics. 2014. Lee Ming Ta Michael, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Detection of HLA-B*58:01 with TaqMan assay and its association with allopurinol-induced sCADR. Clinical chemistry and laboratory medicine : CCLM / FESCC. 2014. Zhang Xinju, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Direct PCR: a new pharmacogenetic approach for the inexpensive testing of HLA-B*57:01. The pharmacogenomics journal. 2014. Cascella R, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Insights into the poor prognosis of allopurinol-induced severe cutaneous adverse reactions: the impact of renal insufficiency, high plasma levels of oxypurinol and granulysin. Annals of the rheumatic diseases. 2014. Chung Wen-Hung, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP2C9 and HLA-B Genotype and Phenytoin Dosing. Clinical pharmacology and therapeutics. 2014. Caudle Kelly E, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genetic variants associated with phenytoin-related severe cutaneous adverse reactions. JAMA : the journal of the American Medical Association. 2014. Chung Wen-Hung, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cost-effectiveness analysis of HLA-B5801 genotyping in the treatment of gout patients with chronic renal insufficiency in Korea. Arthritis care & research. 2014. Park Dong-Jin, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA Class I restricted CD8+ and Class II restricted CD4+ T cells are implicated in the pathogenesis of nevirapine hypersensitivity. AIDS (London, England). 2014. Keane Niamh M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: uric acid-lowering drugs pathway, pharmacodynamics. Pharmacogenetics and genomics. 2014. McDonagh Ellen M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Diagnostic accuracy of HLA-B*57:01 screening for the prediction of abacavir hypersensitivity and clinical utility of the test: a meta-analytic review. Pharmacogenomics. 2014. Cargnin Sarah, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Oxypurinol directly and immediately activates the drug-specific T cells via the preferential use of HLA-B*58:01. Journal of immunology (Baltimore, Md. : 1950). 2014. Yun James, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pharmacogenetics of antiepileptic drug-induced hypersensitivity. Pharmacogenomics. 2014. Bloch Katarzyna M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Fine Mapping Seronegative and Seropositive Rheumatoid Arthritis to Shared and Distinct HLA Alleles by Adjusting for the Effects of Heterogeneity. American journal of human genetics. 2014. Han Buhm, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 update. Clinical pharmacology and therapeutics. 2014. Martin Michael A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association of HLA-B*1502 and *1511 allele with antiepileptic drug-induced Stevens-Johnson syndrome in central China. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban. 2014. Sun Dan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genotype-phenotype association between HLA and carbamazepine-induced hypersensitivity reactions: strength and clinical correlations. Journal of dermatological science. 2014. Hsiao Yi-Hsin, et al. PubMed
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Building pharmacogenetics into a pharmacovigilance program in Singapore: using serious skin rash as a pilot study. The pharmacogenomics journal. 2014. Toh D S L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA alleles and hypersensitivity to carbamazepine: an updated systematic review with meta-analysis. Pharmacogenetics and genomics. 2013. Grover Sandeep, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cost-effectiveness analysis of HLA-B*5801 testing in preventing allopurinol-induced SJS/TEN in Thai population. PloS one. 2014. Saokaew Surasak, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genetic diversity of the KIR/HLA system and outcome of patients with metastatic colorectal cancer treated with chemotherapy. PloS one. 2014. De Re Valli, et al. PubMed
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HLA-DR9 and DR14 Are Associated with the Allopurinol-Induced Hypersensitivity in Hematologic Malignancy. The Tohoku journal of experimental medicine. 2014. Jung Jae-Woo, et al. PubMed
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HLA-A*31:01 and different types of carbamazepine-induced severe cutaneous adverse reactions: an international study and meta-analysis. The pharmacogenomics journal. 2013. Genin E, et al. PubMed
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Association of carbamazepine-induced severe cutaneous drug reactions and HLA-B*1502 allele status, and dose and treatment duration in paediatric neurology patients in Singapore. Archives of disease in childhood. 2013. Chong Kok Wee, et al. PubMed
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Allopurinol hypersensitivity is primarily mediated by dose-dependent oxypurinol-specific T cell response. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2013. Yun J, et al. PubMed
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Specific HLA types are associated with antiepileptic drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese subjects. Pharmacogenomics. 2013. Kaniwa Nahoko, et al. PubMed
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Association between HLA-B*1301 and dapsone-induced hypersensitivity reactions among leprosy patients in China. The Journal of investigative dermatology. 2013. Wang Hongsheng, et al. PubMed
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A weighted genetic risk score using all known susceptibility variants to estimate rheumatoid arthritis risk. Annals of the rheumatic diseases. 2013. Yarwood Annie, et al. PubMed
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HLA-B*13:01 and the dapsone hypersensitivity syndrome. The New England journal of medicine. 2013. Zhang F-R, et al. PubMed
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Predictive markers for carbamazepine and lamotrigine-induced maculopapular exanthema in Han Chinese. Epilepsy research. 2013. Li Li-Juan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Relationship between the HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. JAMA dermatology. 2013. Tangamornsuksan Wimonchat, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-B*58:01 is a risk factor for allopurinol-induced DRESS and Stevens-Johnson syndrome/toxic epidermal necrolysis in a Portuguese population. The British journal of dermatology. 2013. Gonçalo M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-B*58:01 strongly associates with allopurinol-induced adverse drug reactions in a Japanese sample population. Journal of dermatological science. 2013. Niihara Hiroyuki, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-A*31:01 and HLA-B*15:02 as Genetic Markers for Carbamazepine Hypersensitivity in Children. Clinical pharmacology and therapeutics. 2013. Amstutz U, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-B alleles associated with severe cutaneous reactions to antiepileptic drugs in Han Chinese. Epilepsia. 2013. Cheung Ying-Kit, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for HLA-B Genotype and Carbamazepine Dosing. Clinical pharmacology and therapeutics. 2013. Leckband Susan G, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Phenobarbital-induced severe cutaneous adverse drug reactions are associated with CYP2C19*2 in Thai children. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2013. Manuyakorn Wiparat, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Human leukocyte antigen class I alleles can predict response to pegylated interferon/ribavirin therapy in chronic hepatitis C Egyptian patients. Archives of Iranian medicine. 2013. Farag Raghda E, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Associations between HLA-DRB1*0102, HLA-B*5801, and hepatotoxicity during initiation of nevirapine-containing regimens in South Africa. Journal of acquired immune deficiency syndromes (1999). 2013. Phillips Elizabeth, et al. PubMed
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Lamotrigine-induced hypersensitivity syndrome in a Han Chinese patient with the HLA-B 5801 genotype. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2013. Chow Julie Chi, et al. PubMed
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HLA-B*5801 should be used to screen for risk of Stevens-Johnson syndrome in family members of Han Chinese patients commencing allopurinol therapy. The Journal of rheumatology. 2013. Lee Ming-Han Hugo, et al. PubMed
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The association between oxcarbazepine-induced maculopapular eruption and HLA-B alleles in a northern Han Chinese population. BMC neurology. 2013. Lv Yu-Dan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association between the HLA-B*15:02 allele and carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in Han individuals of northeastern China. Pharmacological reports : PR. 2013. He Xiao-Jing, et al. PubMed
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Allopurinol-induced drug rash with eosinophilia and systemic symptoms mimicking acute generalized exanthematous pustulosis. The Journal of dermatology. 2012. Huang Yu Chen, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Human leukocyte antigens (HLA) associated drug hypersensitivity: consequences of drug binding to HLA. Allergy. 2012. Yun J, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA Genotype and Carbamazepine-Induced Cutaneous Adverse Drug Reactions: A Systematic Review. Clinical pharmacology and therapeutics. 2012. Yip V L, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Cutaneous adverse drug reactions to allopurinol: 10 year observational survey of the dermatology department--Cagliari University (Italy). Journal of the European Academy of Dermatology and Venereology : JEADV. 2012. Atzori L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomics in clinical practice and drug development. Nature biotechnology. 2012. Harper Andrew R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia. Arthritis care & research. 2012. Khanna Dinesh, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical Pharmacogenetics Implementation Consortium Guidelines for Human Leukocyte Antigen-B Genotype and Allopurinol Dosing. Clinical pharmacology and therapeutics. 2012. Hershfield M S, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Potential effect of pharmacogenetics on maternal, fetal and infant antiretroviral drug exposure during pregnancy and breastfeeding. Pharmacogenomics. 2012. Olagunju Adeniyi, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Cutaneous reactions induced by oxcarbazepine in Southern Han Chinese: incidence, features, risk factors and relation to HLA-B alleles. Seizure : the journal of the British Epilepsy Association. 2012. He Na, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Severe drug-induced hypersensitivity syndrome with a shared HLA-B allele. The Medical journal of Australia. 2012. Harding Damian J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Predictive Genetic Testing for Drug-Induced Liver Injury: Considerations of Clinical Utility. Clinical pharmacology and therapeutics. 2012. Alfirevic A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association between HLA and Stevens-Johnson syndrome induced by carbamazepine in Southern Han Chinese: genetic markers besides B*1502?. Basic & clinical pharmacology & toxicology. 2012. Shi Yi-Wu, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-B*58:01 allele is associated with augmented risk for both mild and severe cutaneous adverse reactions induced by allopurinol in Han Chinese. Pharmacogenomics. 2012. Cao Zhi-Hao, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association between HLA-B*58:01 allele and severe cutaneous adverse reactions with allopurinol in Han Chinese in Hong Kong. The British journal of dermatology. 2012. Chiu M L S, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genetic and immune predictors for hypersensitivity syndrome to antiepileptic drugs. Translational research : the journal of laboratory and clinical medicine. 2012. Neuman Manuela G, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-B*1502 strongly predicts carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Thai patients with neuropathic pain. Pain practice : the official journal of World Institute of Pain. 2012. Kulkantrakorn Kongkiat, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing. Clinical pharmacology and therapeutics. 2012. Martin M A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Human leukocyte antigen (HLA) and pharmacogenetics: screening for HLA-B*57:01 among human immunodeficiency virus-positive patients from southern Alberta. Human immunology. 2012. Berka Noureddine, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Drug hypersensitivity and human leukocyte antigens of the major histocompatibility complex. Annual review of pharmacology and toxicology. 2012. Bharadwaj Mandvi, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Allopurinol pharmacogenetics: assessment of potential clinical usefulness. Pharmacogenomics. 2011. Zineh Issam, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-B*1502 allele is associated with a cross-reactivity pattern of cutaneous adverse reactions to antiepileptic drugs. The Journal of international medical research. 2012. Wang J, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Carbamazepine-induced severe cutaneous adverse reactions and HLA genotypes in Koreans. Epilepsy research. 2011. Kim Sae-Hoon, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Frequency of the HLA-B*1502 allele contributing to carbamazepine-induced hypersensitivity reactions in a cohort of Malaysian epilepsy patients. Asian Pacific journal of allergy and immunology / launched by the Allergy and Immunology Society of Thailand. 2011. Then Sue-Mian, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in mainland Han Chinese patients. European journal of clinical pharmacology. 2011. Zhang Yan, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A whole-genome association study of major determinants for allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients. The pharmacogenomics journal. 2011. Tohkin M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A study of HLA class I and class II 4-digit allele level in Stevens-Johnson syndrome and toxic epidermal necrolysis. International journal of immunogenetics. 2011. Cristallo A F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Hla-B alleles and lamotrigine-induced cutaneous adverse drug reactions in the Han Chinese population. Basic & clinical pharmacology & toxicology. 2011. Shi Yi-Wu, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genetic predisposition to oxcarbazepine induced Stevens-Johnson syndrome. Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine. 2011. Wal Pranay, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Initiating allopurinol therapy: do we need to know the patient's HLA status?. Internal medicine journal. 2011. Lee Ming-Han H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genome-Wide Association study of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Europe. Orphanet journal of rare diseases. 2011. Genin Emmanuelle, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
PharmGKB summary: carbamazepine pathway. Pharmacogenetics and genomics. 2011. Thorn Caroline F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Prospective-retrospective biomarker analysis for regulatory consideration: white paper from the industry pharmacogenomics working group. Pharmacogenomics. 2011. Patterson Scott D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomics: the genetics of variable drug responses. Circulation. 2011. Roden Dan M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association of the genetic marker for abacavir hypersensitivity HLA-B*5701 with HCP5 rs2395029 in Mexican Mestizos. Pharmacogenomics. 2011. Sanchez-Giron Francisco, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-B58 can help the clinical decision on starting allopurinol in patients with chronic renal insufficiency. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2011. Jung Jae-Woo, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association between HLA-B*1502 allele and carbamazepine-induced severe cutaneous adverse reactions in Han people of southern China mainland. Seizure : the journal of the British Epilepsy Association. 2011. Wang Qian, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Pilot association study of oxcarbazepine-induced mild cutaneous adverse reactions with HLA-B*1502 allele in Chinese Han population. Seizure : the journal of the British Epilepsy Association. 2011. Hu Fa-yun, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Stevens-Johnson syndrome induced by acetazolamide. The Journal of dermatology. 2011. Her Young, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Carbamazepine-induced toxic effects and HLA-B*1502 screening in Taiwan. The New England journal of medicine. 2011. Chen Pei, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genomics and drug response. The New England journal of medicine. 2011. Wang Liewei, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-B*1502 genotyping in two Chinese patients with phenytoin-induced Stevens-Johnson syndrome. Epilepsy & behavior : E&B. 2011. Min Fu-Li, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association of HLA-B*1502 allele with carbamazepine-induced toxic epidermal necrolysis and Stevens-Johnson syndrome in the multi-ethnic Malaysian population. International journal of dermatology. 2011. Chang Choong-Chor, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Positive and negative associations of HLA class I alleles with allopurinol-induced SCARs in Koreans. Pharmacogenetics and genomics. 2011. Kang Hye-Ryun, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Phenytoin-induced Stevens-Johnson syndrome with negative HLA-B*1502 allele in mainland China: Two cases. Seizure : the journal of the British Epilepsy Association. 2011. Hu Fa-Yun, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Distribution of HLA-B alleles in a Ugandan HIV-infected adult population: NORA pharmacogenetic substudy of DART. Tropical medicine & international health : TM & IH. 2011. Munderi Paula, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Practical recommendations for pharmacogenomics-based prescription: 2010 ESF-UB Conference on Pharmacogenetics and Pharmacogenomics. Pharmacogenomics. 2011. Becquemont Laurent, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association of HLA-B*5801 allele and allopurinol-induced Stevens Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. BMC medical genetics. 2011. Somkrua Ratchadaporn, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Breaking Barriers in the Genomics and Pharmacogenetics of Drug Addiction. Clinical pharmacology and therapeutics. 2010. Ho M K, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-B*1511 is a risk factor for carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Japanese patients. Epilepsia. 2010. Kaniwa Nahoko, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Association study of lamotrigine-induced cutaneous adverse reactions and HLA-B*1502 in a Han Chinese population. Epilepsy research. 2010. An Dong-Mei, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association between carbamazepine-induced cutaneous adverse drug reactions and the HLA-B*1502 allele among patients in central China. Epilepsy & behavior : E&B. 2010. Wu X T, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Systematic review of pharmacoeconomic studies of pharmacogenomic tests. Pharmacogenomics. 2010. Beaulieu Mathieu, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Characterization of 107 genomic DNA reference materials for CYP2D6, CYP2C19, CYP2C9, VKORC1, and UGT1A1: a GeT-RM and Association for Molecular Pathology collaborative project. The Journal of molecular diagnostics : JMD. 2010. Pratt Victoria M, et al. PubMed
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HLA-B*5901 is strongly associated with methazolamide-induced Stevens-Johnson syndrome/toxic epidermal necrolysis. Pharmacogenomics. 2010. Kim Sae-Hoon, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population. Epilepsia. 2010. Tassaneeyakul Wichittra, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Drug-induced liver injury: past, present and future. Pharmacogenomics. 2010. Daly Ann K. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Common risk allele in aromatic antiepileptic-drug induced Stevens-Johnson syndrome and toxic epidermal necrolysis in Han Chinese. Pharmacogenomics. 2010. Hung Shuen-Iu, et al. PubMed
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HLA class I markers in Japanese patients with carbamazepine-induced cutaneous adverse reactions. Epilepsia. 2010. Ikeda Hiroko, et al. PubMed
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Pharmacogenetics of antiretrovirals. Antiviral research. 2010. Tozzi Valerio. PubMed
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Genetic determinants of HIV-1 infection and progression to AIDS: immune response genes. Tissue antigens. 2009. Kaur G, et al. PubMed
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HLA-B27 and HLA-B51 determination in Tunisian healthy subjects and patients with suspected ankylosing spondylitis and Behçet's disease. Annals of the New York Academy of Sciences. 2009. Sakly Nabil, et al. PubMed
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High-resolution HLA genotyping and severe cutaneous adverse reactions in lamotrigine-treated patients. Pharmacogenetics and genomics. 2009. Kazeem Gbenga R, et al. PubMed
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Strong association between HLA-B*5801 and allopurinol-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in a Thai population. Pharmacogenetics and genomics. 2009. Tassaneeyakul Wichittra, et al. PubMed
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HLA B27 as predisposition factor to suffer age related macular degeneration. Cellular & molecular immunology. 2009. Villegas Becerril Enrique, et al. PubMed
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Multiple Loci within the major histocompatibility complex confer risk of psoriasis. PLoS genetics. 2009. Feng Bing-Jian, et al. PubMed
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HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nature genetics. 2009. Daly Ann K, et al. PubMed
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Oxcarbazepine-induced Stevens-Johnson syndrome in a patient with HLA-B*1502 genotype. Journal of the European Academy of Dermatology and Venereology : JEADV. 2009. Chen Y-C, et al. PubMed
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Human leukocyte antigen frequency in human high-grade gliomas: a case-control study in Sicily. Neurosurgery. 2009. La Torre Domenico, et al. PubMed
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Human leukocyte antigen-related risk factors for toxic epidermal necrosis. The Pediatric infectious disease journal. 2009. Kemen Christoph, et al. PubMed
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HLA-B is the best candidate of susceptibility genes in HLA for Japanese ulcerative colitis. Tissue antigens. 2009. Aizawa H, et al. PubMed
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Epilepsy pharmacogenetics. Pharmacogenomics. 2009. Kasperavici¿te Dalia, et al. PubMed
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Confirmation of HLA class II independent type 1 diabetes associations in the major histocompatibility complex including HLA-B and HLA-A. Diabetes, obesity & metabolism. 2009. Howson J M M, et al. PubMed
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HLA-B*3505 allele is a strong predictor for nevirapine-induced skin adverse drug reactions in HIV-infected Thai patients. Pharmacogenetics and genomics. 2009. Chantarangsu Soranun, et al. PubMed
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Oxcarbazepine-induced Stevens-Johnson syndrome: a case report. The Kaohsiung journal of medical sciences. 2009. Lin Lung-Chang, et al. PubMed
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Genome-wide approaches to identify pharmacogenetic contributions to adverse drug reactions. The pharmacogenomics journal. 2009. Nelson M R, et al. PubMed
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The clinical impact of pharmacogenetics on the treatment of epilepsy. Epilepsia. 2009. Löscher Wolfgang, et al. PubMed
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Carbamazepine and phenytoin induced Stevens-Johnson syndrome is associated with HLA-B*1502 allele in Thai population. Epilepsia. 2008. Locharernkul Chaichon, et al. PubMed
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Evolution and selection of human leukocyte antigen alleles by Plasmodium falciparum infection. Human immunology. 2008. Ghosh Kanjaksha. PubMed
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Association of HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome among Indians. Indian journal of dermatology, venereology and leprology. 2009. Mehta Timir Y, et al. PubMed
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FDA: Epilepsy drugs may carry skin risks for Asians. JAMA : the journal of the American Medical Association. 2008. Kuehn Bridget M. PubMed
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HLA-B locus in Japanese patients with anti-epileptics and allopurinol-related Stevens-Johnson syndrome and toxic epidermal necrolysis. Pharmacogenomics. 2008. Kaniwa Nahoko, et al. PubMed
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Carbamazepine, HLA-B*1502 and risk of Stevens-Johnson syndrome and toxic epidermal necrolysis: US FDA recommendations. Pharmacogenomics. 2008. Ferrell P Brent, et al. PubMed
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Genetic variation in drug transporters in ethnic populations. Clinical pharmacology and therapeutics. 2008. Cropp C D, et al. PubMed
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The HCP5 single-nucleotide polymorphism: a simple screening tool for prediction of hypersensitivity reaction to abacavir. The Journal of infectious diseases. 2008. Colombo Sara, et al. PubMed
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Clozapine-induced agranulocytosis and its genetic determinants. Pharmacogenomics. 2008. Opgen-Rhein Carolin, et al. PubMed
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Pharmacogenomics of antiretrovirals. Recent patents on anti-infective drug discovery. 2008. Roca Bernardino. PubMed
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Pharmacogenetics of antiretroviral agents. Current opinion in HIV and AIDS. 2008. Owen Andrew, et al. PubMed
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A European study of HLA-B in Stevens-Johnson syndrome and toxic epidermal necrolysis related to five high-risk drugs. Pharmacogenetics and genomics. 2008. Lonjou Christine, et al. PubMed
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Pharmacogenetic information derived from analysis of HLA alleles. Pharmacogenomics. 2008. Gatanaga Hiroyuki, et al. PubMed
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HLA-B*5701 screening for hypersensitivity to abacavir. The New England journal of medicine. 2008. Mallal Simon, et al. PubMed
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Ticlopidine-induced hepatotoxicity is associated with specific human leukocyte antigen genomic subtypes in Japanese patients: a preliminary case-control study. The pharmacogenomics journal. 2008. Hirata K, et al. PubMed
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HLA-B allele associations with certain drugs are not confirmed in Japanese patients with severe cutaneous drug reactions. Acta dermato-venereologica. 2008. Kano Yoko, et al. PubMed
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HLA-B*1301 as a biomarker for genetic susceptibility to hypersensitivity dermatitis induced by trichloroethylene among workers in China. Environmental health perspectives. 2007. Li Haishan, et al. PubMed
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HLA-B*5701 clinical testing: early experience in the United States. Pharmacogenetics and genomics. 2007. Faruki Hawazin, et al. PubMed
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[Study on correlation between HLA-A, B, DR alleles and Duchenne muscular dystrophy]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2007. Chen Wei, et al. PubMed
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Human leukocyte antigens and drug hypersensitivity. Current opinion in allergy and clinical immunology. 2007. Chung Wen-Hung, et al. PubMed
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A whole-genome association study of major determinants for host control of HIV-1. Science (New York, N.Y.). 2007. Fellay Jacques, et al. PubMed
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Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese. Epilepsia. 2007. Man Celeste B L, et al. PubMed
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Stevens-Johnson syndrome, drug-induced hypersensitivity syndrome and toxic epidermal necrolysis caused by allopurinol in patients with a common HLA allele: what causes the diversity?. Dermatology (Basel, Switzerland). 2007. Dainichi Teruki, et al. PubMed
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HLA-B locus in Caucasian patients with carbamazepine hypersensitivity. Pharmacogenomics. 2006. Alfirevic Ana, et al. PubMed
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[Disequilibrium linkage between the polymorphism in exons 2, 3 and 4 of the MICA gene and HLA-B antigen of patient with ankylosing spondylitis]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics. 2006. Su Hong, et al. PubMed
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Genetic susceptibility to carbamazepine-induced cutaneous adverse drug reactions. Pharmacogenetics and genomics. 2006. Hung Shuen-Iu, et al. PubMed
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A marker for Stevens-Johnson syndrome ...: ethnicity matters. The pharmacogenomics journal. 2006. Lonjou C, et al. PubMed
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Overview of the pharmacogenetics of HIV therapy. The pharmacogenomics journal. 2006. Rodríguez-Nóvoa S, et al. PubMed
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[Correlation between the polymorphism of HLA-A, -B, and -DRB1 alleles and susceptibility to leukemia]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology. 2005. Zhou Lan-xia, et al. PubMed
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HLA-B*5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proceedings of the National Academy of Sciences of the United States of America. 2005. Hung Shuen-Iu, et al. PubMed
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Cost-effectiveness analysis of HLA B*5701 genotyping in preventing abacavir hypersensitivity. Pharmacogenetics. 2004. Hughes Dyfrig A, et al. PubMed
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Medical genetics: a marker for Stevens-Johnson syndrome. Nature. 2004. Chung Wen-Hung, et al. PubMed
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HLA class I B44 is associated with sustained response to interferon + ribavirin therapy in patients with chronic hepatitis C. The American journal of gastroenterology. 2003. Romero-Gómez Manuel, et al. PubMed
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Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002. Mallal S, et al. PubMed
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The lower susceptibility to Plasmodium falciparum malaria of Fulani of Burkina Faso (west Africa) is associated with low frequencies of classic malaria-resistance genes. Transactions of the Royal Society of Tropical Medicine and Hygiene. 2001. Modiano D, et al. PubMed
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Stevens-Johnson syndrome induced by methazolamide treatment. Archives of ophthalmology. 1997. Shirato S, et al. PubMed
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Common west African HLA antigens are associated with protection from severe malaria. Nature. 1991. Hill A V, et al. PubMed
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HLA typing in birdshot chorioretinopathy. American journal of ophthalmology. 1988. Priem H A, et al. PubMed