Gene:
HLA-DQA1
major histocompatibility complex, class II, DQ alpha 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.

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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 *01:02:01:01 N/A N/A N/A
No VIP available CA VA *02:01 N/A N/A N/A
No VIP available CA VA
rs9272105 32341820A>A, 32539999G>A, 32599999G>A, 3836834A>A, 3881721G>A, 3938863G>A, 4033445G>A, 4050375A>A, 4056154G>A
G > A
Not Available
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  None
Alternate Symbols:  CELIAC1
PharmGKB Accession Id: PA35066

Details

Cytogenetic Location: chr6 : p21.32 - p21.32
GP mRNA Boundary: chr6 : 32605183 - 32611429
GP Gene Boundary: chr6 : 32595183 - 32614429
Strand: plus
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.

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-DQA1: 12

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
HLA-DQA1-HLA-DRB1 variants confer susceptibility to pancreatitis induced by thiopurine immunosuppressants. Nature genetics. 2014. Heap Graham 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
HLA-DQ strikes again: Genome-wide association study further confirms HLA-DQ in the diagnosis of asthma among adults. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. 2012. Lasky-Su 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 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
A fresh look at the mechanism of isoniazid-induced hepatotoxicity. Clinical pharmacology and therapeutics. 2011. Metushi I G, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Single-nucleotide polymorphisms in HLA- and non-HLA genes associated with the development of antibodies to interferon-beta therapy in multiple sclerosis patients. The pharmacogenomics journal. 2011. Weber F, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
HLA-DQA1*02:01 is a major risk factor for lapatinib-induced hepatotoxicity in women with advanced breast cancer. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2011. Spraggs Colin F, 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
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
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 2007. Wellcome Trust Case Control Consortium. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Evaluation of clinical and immunogenetic risk factors for the development of hepatotoxicity during antituberculosis treatment. American journal of respiratory and critical care medicine. 2002. Sharma Surendra 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
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