Gene:
HLA-DRB1
major histocompatibility complex, class II, DR beta 1

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

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 10/27/2013

European Medicines Agency (EMA) Label for lapatinib and ERBB2, HLA-DQA1, HLA-DRB1

Genetic testing required

Summary

The EMA European Public Assessment Report (EPAR) for lapatinib (Tyverb) contains pharmacogenetic information regarding the indication of the drug in HER2+ (ERBB2) breast cancer, and that HER2 status should be determined using an accurate technique. It also contains pharmacogenetic information regarding an increased risk of drug-induced hepatotoxicity in patients carrying the DQA1*02:01 or DRB1*07:01 HLA alleles.

Annotation

Excerpts from the lapatinib (Tyverb) EPAR:

Tyverb is indicated for the treatment of patients with breast cancer, whose tumours overexpress HER2 (ErbB2).


Lapatinib inhibits ErbB-driven tumour cell growth in vitro and in various animal models.


HER2 (ErbB2) overexpressing tumours are defined by IHC3+, or IHC2+ with gene amplification or gene amplification alone. HER2 status should be determined using accurate and validated methods.


Patients who carry the HLA alleles DQA1*02:01 and DRB1*07:01 have increased risk of Tyverb-associated hepatotoxicity. In a large, randomised clinical trial of Tyverb monotherapy (n=1,194), the cumulative frequency of severe liver injury (ALT >5 times the upper limit of normal, NCI CTCAE grade 3) at 1 year of treatment was 2.8% overall.

This information is highlighted in the following sections:
Therapeutic indications, posology and method of administration, special warnings and precautions for use, package leaflet: information for the user.

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the lapatinib (Tyverb) EMA drug label.

*Disclaimer: The contents of this page have not been endorsed by the EMA and are the sole responsibility of PharmGKB.


PharmGKB contains no Clinical Variants that meet the highest level of criteria.

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?

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 *01:01:01 N/A N/A N/A
No VIP available No VIP available VA *01:02:01 N/A N/A N/A
No VIP available CA VA *03:01 N/A N/A N/A
No VIP available No VIP available VA *03:01:01:01 N/A N/A N/A
No VIP available No VIP available VA *04:10:01 N/A N/A N/A
No VIP available No VIP available VA *07:01:01:01 N/A N/A N/A
No VIP available No VIP available VA *08:03:02 N/A N/A N/A
No VIP available CA VA *09:01:02 N/A N/A N/A
No VIP available No VIP available VA *11:01:01 N/A N/A N/A
No VIP available No VIP available VA *12:02:01 N/A N/A N/A
No VIP available CA VA *14:01:01 N/A N/A N/A
No VIP available No VIP available VA *14:05:01 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 No VIP available VA *16:02:01 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: PA35072

Details

Cytogenetic Location: chr6 : p21.32 - p21.32
GP mRNA Boundary: chr6 : 32546546 - 32557562
GP Gene Boundary: chr6 : 32543546 - 32567562
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.

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.

The following were added by PharmGKB to aid curation and reflect how the vast majority of studies report the alleles:
*03:01

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.

No related genes are available

Curated Information ?

Curated Information ?

Publications related to HLA-DRB1: 46

No Dosing Guideline available No Drug Label available No Clinical Annotation available 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
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 CA VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
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 No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
HLA-DRB1*1501 and VDR polymorphisms and survival of Mycobacterium tuberculosis in human macrophages exposed to inhalable microparticles. Pharmacogenomics. 2013. Singh Amit K, 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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Identification of the NF-κB activating protein-like locus as a risk locus for rheumatoid arthritis. Annals of the rheumatic diseases. 2012. Xie Gang, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available 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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenomic update on multiple sclerosis: a focus on actual and new therapeutic strategies. The pharmacogenomics journal. 2012. Foti Cuzzola V, 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
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 No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Increased frequency of DRB1*11:01 in anti-HMG-CoA reductase-associated autoimmune myopathy. Arthritis care & research. 2012. Mammen Andrew L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Allelic combinations of immune-response genes associated with glatiramer acetate treatment response in Russian multiple sclerosis patients. Pharmacogenomics. 2012. Tsareva Ekaterina Y, 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 of toxicity, plasma trough concentration and treatment outcome with nevirapine-containing regimen in anti-retroviral-naïve HIV-infected adults: an exploratory study of the TRIANON ANRS 081 trial. Basic & clinical pharmacology & toxicology. 2011. Gozalo Claire, 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
Differentially expressed genes in human peripheral blood as potential markers for statin response. Journal of molecular medicine (Berlin, Germany). 2011. Won Hong-Hee, 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
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 No Variant Annotation available No VIP available No VIP available
Susceptibility to amoxicillin-clavulanate-induced liver injury is influenced by multiple HLA class I and II alleles. Gastroenterology. 2011. Lucena M Isabel, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A genome-wide study identifies HLA alleles associated with lumiracoxib-related liver injury. Nature genetics. 2010. Singer Jonathan B, 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 No Clinical Annotation available 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
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: insights from genetic studies. Pharmacogenomics. 2009. Andrade Raúl 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
Human leukocyte antigen frequency in human high-grade gliomas: a case-control study in Sicily. Neurosurgery. 2009. La Torre Domenico, 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
TNF, LTA, HSPA1L and HLA-DR gene polymorphisms in HIV-positive patients with hypersensitivity to cotrimoxazole. Pharmacogenomics. 2009. Alfirevic Ana, 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
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Evolution and selection of human leukocyte antigen alleles by Plasmodium falciparum infection. Human immunology. 2008. Ghosh Kanjaksha. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
HLA-DRB1*0401 and HLA-DRB1*0408 are strongly associated with the development of antibodies against interferon-beta therapy in multiple sclerosis. American journal of human genetics. 2008. Hoffmann Steve, 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
Clozapine-induced agranulocytosis and its genetic determinants. Pharmacogenomics. 2008. Opgen-Rhein Carolin, 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 pharmacogenetic investigation of a hepatic adverse event without clinical signs of immunopathology suggests an underlying immune pathogenesis. The pharmacogenomics journal. 2008. Kindmark A, 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
Pharmacogenetic information derived from analysis of HLA alleles. Pharmacogenomics. 2008. Gatanaga Hiroyuki, 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
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis. Nature genetics. 2007. Lundmark Frida, 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
TRAF1-C5 as a risk locus for rheumatoid arthritis--a genomewide study. The New England journal of medicine. 2007. Plenge Robert 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
Risk alleles for multiple sclerosis identified by a genomewide study. The New England journal of medicine. 2007. International Multiple Sclerosis Genetics Consortium, 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
[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
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The influence of genetic variation in the HLA-DRB1 and LTA-TNF regions on the response to treatment of early rheumatoid arthritis with methotrexate or etanercept. Arthritis and rheumatism. 2004. Criswell Lindsey A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
HLA association in aspirin-intolerant asthma: DPB1*0301 as a strong marker in a Korean population. The Journal of allergy and clinical immunology. 2004. Choi Jeong Hee, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
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
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Differential surface expression of HLA-DRB1 and HLA-DRB4 among peripheral blood cells of DR4 positive individuals. Human immunology. 1999. Czerwony G, 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 significance of HLA-DRB1*0410 in Japanese patients with idiopathic thrombocytopenic purpura. Blood. 1998. Nomura 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
Immune mechanism of aplastic anemia. International journal of hematology. 1997. Nakao S. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Aspirin-induced asthma and HLA-DRB1 and HLA-DPB1 genotypes. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 1997. Dekker J W, 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
Common west African HLA antigens are associated with protection from severe malaria. Nature. 1991. Hill A V, et al. PubMed

LinkOuts

Entrez Gene:
3123
OMIM:
126200
142857
180300
181000
UCSC Genome Browser:
NM_002124
RefSeq RNA:
NM_002124
RefSeq Protein:
NP_002115
MutDB:
HLA-DRB1
HuGE:
HLA-DRB1
Comparative Toxicogenomics Database:
3123
ModBase:
P01912
P13761
P20039
Q30167
Q5Y7B9
Q5Y7E9
Q9BCP2
Q9MY13
Q9TQE0
HGNC:
4948

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