Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 May 17:2016:baw069.
doi: 10.1093/database/baw069. Print 2016.

A web resource for mining HLA associations with adverse drug reactions: HLA-ADR

Gurpreet S Ghattaoraya  1 , Yenal Dundar  2 , Faviel F González-Galarza  3 , Maria Helena Thomaz Maia  4 , Eduardo José Melo Santos  5 , Andréa Luciana Soares da Silva  4 , Antony McCabe  6 , Derek Middleton  7 , Ana Alfirevic  8 , Rumona Dickson  9 , Andrew R Jones  10
Affiliations

A web resource for mining HLA associations with adverse drug reactions: HLA-ADR

Gurpreet S Ghattaoraya et al. Database (Oxford). .

Abstract

Human leukocyte antigens (HLA) are an important family of genes involved in the immune system. Their primary function is to allow the host immune system to be able to distinguish between self and non-self peptides-e.g. derived from invading pathogens. However, these genes have also been implicated in immune-mediated adverse drug reactions (ADRs), presenting a problem to patients, clinicians and pharmaceutical companies. We have previously developed the Allele Frequency Net Database (AFND) that captures the allelic and haplotype frequencies for these HLA genes across many healthy populations from around the world. Here, we report the development and release of the HLA-ADR database that captures data from publications where HLA alleles and haplotypes have been associated with ADRs (e.g. Stevens-Johnson Syndrome/toxic epidermal necrolysis and drug-induced liver injury). HLA-ADR was created by using data obtained through systematic review of the literature and semi-automated literature mining. The database also draws on data already present in AFND allowing users to compare and analyze allele frequencies in both ADR patients and healthy populations. The HLA-ADR database provides clinicians and researchers with a centralized resource from which to investigate immune-mediated ADRs.Database URL: http://www.allelefrequencies.net/hla-adr/.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
PRISMA 2009 Flow demonstrating the procedures followed for including data sets in HLA-ADR.
Figure 2.
Figure 2.
Screenshot of the HLA-ADR query page. Users can query the database via the use of filters. They may choose to see associations for genes/alleles, drugs, patient ethnicity, level of significance (P values) and the country/region where the study was conducted.
Figure 3.
Figure 3.
A, Screenshot of the results page where ‘abacavir’ was used as the search criteria. The results show the PubMed/MEDLINE link, the drug featured in the study, the tested allele for the associations, the patient/control cohort ethnicity, the statistical evidence, links to ‘More Details’ and AFND worldwide distributions for that allele. B, A screenshot generated by AFND showing worldwide distributions for the queried allele (e.g. HLA-B*57:01 for abacavir hypersensitivity). This page will be displayed by clicking on the allele distribution link seen in A.
Figure 4.
Figure 4.
Screenshot of the AFND ADR reports page from a search for drug = aspirin, with the other options remaining at their default settings (P < 0.05 and no restrictions on patient ethnicity). A link is provided to the DrugBank page for the drug underneath the search bar. Much like the HLA-ADR query page, the summary table of results show the PubMed/MEDLINE link, the associated allele, the statistical data and a link to the ‘More details’ page where full details about the association can be found. In addition, a ‘risk/protective’ allele assignment is given (red or green box) based on the proportion of carriers of the allele in the patients group compared with the control group.
See this image and copyright information in PMC

References

    1. Kongkaew C., Hann M., Mandal J. et al. (2013) Risk factors for hospital admissions associated with adverse drug events. Pharmacotherapy, 33, 827–837. - PubMed
    1. Pirmohamed M., James S., Meakin S. et al. (2004) Adverse drug reactions as cause of admission to hospital: prospective analysis of 18,820 patients. Br. Med. J., 329, 15–19. - PMC - PubMed
    1. Lexchin J. (2015) How safe are new drugs? Market withdrawal of drugs approved in Canada between 1990 and 2009. Open Medi., 8, e14–e19. - PMC - PubMed
    1. McNaughton R., Huet G., Shakir S. (2014) An investigation into drug products withdrawn from the EU market between 2002 and 2011 for safety reasons and the evidence used to support the decision-making. BMJ Open, 4, e004221. - PMC - PubMed
    1. Rawlins M., Thompson J. (1977) Pathogenesis of adverse drug reactions David M. Davies. In: Textbook of Adverse Drug Reactions. Oxford: Oxford University Press, p. 10.

Publication types