Journal
PHARMACOGENOMICS
Volume 13, Issue 4, Pages 399-405Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/PGS.11.165
Keywords
epilepsy; GWAS; HLA-A*3101; hypersensitivity; lamotrigine; phenytoin
Categories
Funding
- Medical Research Council [G0400126, G0000934]
- Wellcome Trust [084730, 068545/Z/02]
- UCLH CRDC [F136]
- National Institute for Health Research [08-08-SCC]
- Brainwave - the Irish Epilepsy Association/the Medical Research Charities Group of Ireland/Health Research Board [2009/001]
- National Society for Epilepsy
- Universite Libre de Bruxelles (Belgium) [63574/3.4.620.06 F]
- National Institute of Neurological Disorders [RC2NS070344]
- Health Research Board of Ireland
- Fonds National de la Recherche Scientifique [FC 63574/3.4.620.06 F]
- Fonds Erasme pour la Recherche Medicate
- Medical Research Council [G0400126, G1001799, G0000934] Funding Source: researchfish
- MRC [G0000934, G0400126, G1001799] Funding Source: UKRI
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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.
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