title: Human leucocyte antigen-adverse drug reaction associations: from a perspective of ethnicity.
abstract: 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.
authors.affiliation: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.|Institute of Integrative Biology, University of Liverpool, Liverpool, UK.|Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
authors.forename: G S
authors.identifier: http://orcid.org/0000-0003-4809-7342
authors.initials: GS
authors.lastname: Ghattaoraya
authors.affiliation: Transplant Immunology Laboratory, Royal Liverpool and Broadgreen University Hospital, Liverpool, UK.|Institute of Infection and Global Health, University of Liverpool, Liverpool, UK.
authors.forename: D
authors.initials: D
authors.lastname: Middleton
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool, UK.|Human and Medical Genetics, Institute of Biological Sciences, Federal University of Pará, Belém, Brazil.
authors.forename: E J M
authors.initials: EJ
authors.lastname: Santos
authors.affiliation: Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
authors.forename: R
authors.initials: R
authors.lastname: Dickson
authors.affiliation: Institute of Integrative Biology, University of Liverpool, Liverpool, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Jones
authors.affiliation: Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK.
authors.forename: A
authors.initials: A
authors.lastname: Alfirevic
mesh_terms: D000483:Alleles; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects*; D044466:Asian People; D001424:Bacterial Infections / Q000188:drug therapy / Q000208:ethnology* / Q000235:genetics / Q000276:immunology; D004827:Epilepsy / Q000188:drug therapy / Q000208:ethnology* / Q000235:genetics / Q000276:immunology; D005006:Ethnicity; D005786:Gene Expression Regulation / Q000276:immunology; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006074:Gout Suppressants / Q000008:administration & dosage / Q000009:adverse effects*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000208:ethnology* / Q000235:genetics / Q000276:immunology; D017211:Treatment Failure
chemical_list: D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D006074:Gout Suppressants; D006680:HLA Antigens