Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions. (March 2012)

• Record Type: Journal Article
• Authors: McCormack, Mark; Urban, Thomas J; Shianna, Kevin V; Walley, Nicole; Pandolfo, Massimo; Depondt, Chantal; Chaila, Elijah; O''Conner, Gerard D; Kasperaviččiūūtėė, Dalia; Radtke, Rodney A; Heinzen, Erin L; Sisodiya, Sanjay M; Delanty, Norman; Cavalleri, Gianpiero L
• Is Part Of: Pharmacogenomics. Volume 13:Number 4(2012)
• Page Start: 399
• Page End: 405
• Publication Date: 2012-03
• Subjects: epilepsy -- GWAS -- HLA-A*3101 -- hypersensitivity -- lamotrigine -- phenytoin; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.11.165
• Languages: English
• ISSNs: 1462-2416

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. Original submitted 5 September 2011; Revision submitted 10 November 2011