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 annotates drug labels containing pharmacogenetic information approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), the Pharmaceuticals and Medical Devices Agency, Japan (PMDA), and Health Canada (Santé Canada) (HCSC). PharmGKB annotations provide a brief summary of the PGx in the label, an excerpt from the label and a downloadable highlighted label PDF file. A list of genes and phenotypes found within the label is mapped to label section headers and listed at the end of each annotation. PharmGKB also attempts to interpret the level of action implied in each label with the "PGx Level" tag.

See the legend for more information about drug label sources and PGx Levels.

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



last updated 06/01/2015

FDA Label for lapatinib and ERBB2, HLA-DQA1, HLA-DRB1

Genetic testing required

Summary

The FDA-approved drug label for lapatinib (TYKERB) states that it is indicated for patients with breast cancer whose tumors overexpress HER2 (ERBB2). It also notes that the HLA-DQA1*02:01 and HLA-DRB1*07:01 alleles have been associated with hepatotoxicity in individuals receiving the drug; the label does not discuss genetic testing for the HLA alleles.

There's more of this label. Read more.


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.

There's more of this label. Read more.


last updated 06/08/2015

Health Canada Santé Canada (HCSC) Label for lapatinib and ERBB2, HLA-DQA1, HLA-DRB1

Genetic testing required

Summary

The product monograph for lapatinib (TYKERB) states that it is indicated for patients with metastatic breast cancer whose tumours overexpress HER2. It also notes that those with the HLA-DQA1*02:01 and HLA-DRB1*07:01 alleles have an increased risk of lapatinib-associated hepatotoxicity. The product monograph does not comment on genotyping for the HLA alleles.

There's more of this label. Read more.


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

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.

List of all variant annotations for HLA-DQA1

Variant?
(142)
Alternate Names ? 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 142

Overview

Alternate Names:  HLA-DQA
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

Visualization

UCSC has a Genome Browser that you can use to view PharmGKB annotations for this gene in context with many other sources of information.

View on UCSC Browser
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: 13

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 CA VA No VIP available No VIP available
Prospective validation of HLA-DRB1*07:01 allele carriage as a predictive risk factor for lapatinib-induced liver injury. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2014. Schaid Daniel 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
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 CA 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