title: Pharmacogenetics of antiepileptic drug-induced hypersensitivity.
abstract: Antiepileptic drugs can induce potentially life-threatening hypersensitivity reactions such as Stevens-Johnson syndrome at a frequency of one in 10,000 to one in 1000 treated patients. There is a considerable cross-reactivity among different antiepileptic drugs but the mechanisms are not known. In this review we have summarized current evidence on antiepileptic drug-induced hypersensitivity reactions and performed meta-analyses of published case-control studies that investigated associations between HLA alleles and several antiepileptic drugs in diverse populations. As the heterogeneity between studies was high, we conducted subsequent subgroup analyses and showed that HLA-B*15:02 was associated with carbamazepine, lamotrigine and phenytoin-induced Stevens-Johnson syndrome in Asian populations indicating that pretreatment testing may prevent cross-reactivity. Additionally, we explored the potential of new, high-throughput technologies that may help to understand the mechanisms and predict the risk of adverse drug reactions in the future.
authors.affiliation: The Wolfson Centre for Personalised Medicine, Department of Molecular & Clinical Pharmacology, University of Liverpool, Block A: Waterhouse Buildings, 1-5 Brownlow Street, Liverpool, L69 3GL, UK.
authors.forename: Katarzyna M
authors.initials: KM
authors.lastname: Bloch
authors.forename: Graeme J
authors.initials: GJ
authors.lastname: Sills
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: Ana
authors.initials: A
authors.lastname: Alfirevic
mesh_terms: D000483:Alleles; D000927:Anticonvulsants / Q000009:adverse effects*; D016022:Case-Control Studies; D003429:Cross Reactions / Q000235:genetics; D004342:Drug Hypersensitivity / Q000235:genetics*; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods
chemical_list: D000927:Anticonvulsants
keywords: HLA; antiepileptic drugs; carbamazepine; hypersensitivity reactions; lamotrigine; oxcarbazepine; pharmacogenetics; phenytoin