Human leucocyte antigen–adverse drug reaction associations: from a perspective of ethnicity

• Published in: International journal of immunogenetics Vol. 44; no. 1; pp. 7 - 26
• Main Authors: Ghattaoraya, G. S., Middleton, D., Santos, E. J. M., Dickson, R., Jones, A. R., Alfirevic, A.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-02-2017
• Subjects: Alleles; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anticonvulsants - administration & dosage; Anticonvulsants - adverse effects; Antigens; Asian Continental Ancestry Group; Bacterial Infections - drug therapy; Bacterial Infections - ethnology; Bacterial Infections - genetics; Bacterial Infections - immunology; Consumer protection; Epilepsy - drug therapy; Epilepsy - ethnology; Epilepsy - genetics; Epilepsy - immunology; Ethnic Groups; Ethnicity; Gene Expression Regulation - immunology; Gene Frequency; Genome-Wide Association Study; Gout Suppressants - administration & dosage; Gout Suppressants - adverse effects; Haplotypes; Histocompatibility antigen HLA; HLA Antigens - genetics; HLA Antigens - immunology; Humans; Linkage Disequilibrium; Minority & ethnic groups; Population genetics; Rheumatic Diseases - drug therapy; Rheumatic Diseases - ethnology; Rheumatic Diseases - genetics; Rheumatic Diseases - immunology; Risk factors; Treatment Failure
• ISSN: 1744-3121; 1744-313X
• DOI: 10.1111/iji.12304

Summary
Whilst immune‐mediated adverse drug reactions (ADRs) are rare, they are potentially life‐threatening and present a major problem for clinicians. The underlying mechanisms that cause ADRs are not fully understood although genomewide association studies (GWAS) and case–control investigations have associated human leucocyte antigen (HLA) alleles as risk factors. There is evidence that a patient's ethnic background can have an impact on their risk of developing an ADR. This review summarizes the evidence related to HLA alleles and ADRs with particular focus on patient ethnicity. Our analysis indicated that many of the alleles which have been associated with ADRs are found at higher frequencies in Asian populations. The data also showed that many of the alleles that are reported to be statistically significantly associated with ADRs are in linkage disequilibrium with each other and that they form haplotypes specific to certain ethnicities indicating at least some of the allele associations may not be causal.