C Depondt1, P Godard, R S Espel, A L Da Cruz, P Lienard, M Pandolfo. 1. Laboratory of Experimental Neurology Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Brussels DNAvision, Gosselies, Belgium. Chantal.Depondt@erasme.ulb.ac.be
Abstract
BACKGROUND AND PURPOSE: It is widely acknowledged that individual response to antiepileptic drugs (AEDs) is influenced by genetic factors. However, most of the underlying genes and genetic variants remain unidentified to date. The purpose of this study is to examine the role of common variants in a number of candidate genes in the response to commonly prescribed AEDs. METHODS: We recruited 495 patients with epilepsy. Patients were classified according to their response to several AEDs. We genotyped 104 polymorphisms in 17 candidate genes for AED response. We looked for statistically significant associations between these polymorphisms and well-defined AED response phenotypes. RESULTS: We identified significant associations of CYP2C9 variant alleles with presence of phenytoin (PHT) adverse drug reactions (ADRs) and of GSTM1 copy number variation with the presence of carbamazepine ADRs. The latter association could not be confirmed in a replication study. CONCLUSIONS: Our study is the first comprehensive candidate gene association study in epilepsy pharmacogenetics. Our results confirm the role of CYP2C9 variants in PHT toxicity. No other definite associations were identified. Large-scale efforts are needed to unravel the genetic determinants of AED response.
BACKGROUND AND PURPOSE: It is widely acknowledged that individual response to antiepileptic drugs (AEDs) is influenced by genetic factors. However, most of the underlying genes and genetic variants remain unidentified to date. The purpose of this study is to examine the role of common variants in a number of candidate genes in the response to commonly prescribed AEDs. METHODS: We recruited 495 patients with epilepsy. Patients were classified according to their response to several AEDs. We genotyped 104 polymorphisms in 17 candidate genes for AED response. We looked for statistically significant associations between these polymorphisms and well-defined AED response phenotypes. RESULTS: We identified significant associations of CYP2C9 variant alleles with presence of phenytoin (PHT) adverse drug reactions (ADRs) and of GSTM1 copy number variation with the presence of carbamazepine ADRs. The latter association could not be confirmed in a replication study. CONCLUSIONS: Our study is the first comprehensive candidate gene association study in epilepsy pharmacogenetics. Our results confirm the role of CYP2C9 variants in PHTtoxicity. No other definite associations were identified. Large-scale efforts are needed to unravel the genetic determinants of AED response.
Authors: Ellie H Jhun; Jeffrey L Apfelbaum; David M Dickerson; Sajid Shahul; Randall Knoebel; Keith Danahey; Mark J Ratain; Peter H O'Donnell Journal: Pharmacogenomics Date: 2019-07 Impact factor: 2.638
Authors: Ángel Tito Alvarado; Ana María Muñoz; Berta Loja; Jessica Michiko Miyasato; Jorge Antonio García; Roberto Andrés Cerro; Luis Abel Quiñones; Nelson Miguel Varela Journal: Biomedica Date: 2019-09-01 Impact factor: 0.935