Genome-wide Mapping for Clinically Relevant Predictors of Lamotrigine- and Phenytoin-Induced Hypersensitivity Reactions

Abstract

AIMS: An association between carbamazepine-induced hypersensitivity and HLA-A*3101 has been reported in populations of both European and Asian descent. We aimed to investigate HLA-A*3101 and other common variants across the genome as markers for cutaneous adverse drug reactions (cADRs) attributed to lamotrigine and phenytoin. MATERIALS & METHODS: We recruited patients with lamotrigine-induced cADRs (n = 46) and patients with phenytoin-cADRs (n = 44) and the 1958 British birth cohort was used as a control (n = 1296). HLA-A*3101 was imputed from genome-wide association study data. We applied genome-wide association to study lamotrigine- and phenytoin-induced cADR, and total cADR cases combined. RESULTS: Neither HLA-A*3101 nor any other genetic marker significantly predicted lamotrigine- or phenytoin-induced cADRs. CONCLUSION: HLA-A*3101 does not appear to be a predictor for lamotrigine- and phenytoin-induced cADRs in Europeans. Our genome-wide association study results do not support the existence of a clinically relevant common variant for the development of lamotrigine- or phenytoin-induced cADRs. As a predictive marker, HLA-A*3101 appears to be specific for carbamazepine-induced cADRs.