Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions
- Resource Type
- Academic Journal
- Authors
- McCormack, Mark; Urban, Thomas J; Shianna, Kevin V; Walley, Nicole; Pandolfo, Massimo; Depondt, Chantal; Chaila, Elijah; OʼConner, Gerard D; Kasperavičiūtė, Dalia; Radtke, Rodney A; Heinzen, Erin L; Sisodiya, Sanjay M; Delanty, Norman; Cavalleri, Gianpiero L
- Source
- Pharmacogenomics. Mar 01, 2012 13(4):399-405
- Subject
- Language
- English
- ISSN
- 1462-2416
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.