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/.
Highlights
Adverse drug reactions (ADRs) are a major problem faced by clinicians and pharmaceutical companies, demonstrated by the fact that approximately 6–7% of hospital admissions in the UK have been attributed to ADRs [1, 2]
Because type B reactions only contribute to 20% of all ADRs [11], the manifestations of the adverse reactions may not be observed in patients until the late stages of drug development or after general release, after many patients have been exposed to the drug
The associations covered 16 different types of ADR phenotypes, which were tested against a total of 386 distinct human leukocyte antigen (HLA) alleles (328 high-resolution alleles þ 58 serotype/antigens) in the patient and control cohorts from these studies
Summary
Adverse drug reactions (ADRs) are a major problem faced by clinicians and pharmaceutical companies, demonstrated by the fact that approximately 6–7% of hospital admissions in the UK have been attributed to ADRs [1, 2]. Idiosyncratic or type B ADRs are described as rare, not seen in most people being treated within the standard therapeutic dose range, but can potentially cause severe morbidity and possibly death. They are thought to be immune mediated [6] and in many cases the human leukocyte antigen (HLA) genes have been associated with these reactions [7, 8]. Because type B reactions only contribute to 20% of all ADRs [11], the manifestations of the adverse reactions may not be observed in patients until the late stages of drug development or after general release, after many patients have been exposed to the drug. As well as the risks to patients, the ADRs can lead to post-marketing product withdrawal and significant financial loss due to the huge investment in drug development and manufacturing demands
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