1. A candidate gene study of antiepileptic drug tolerability and efficacy identifies an association of CYP2C9 variants with phenytoin toxicity.
- Author
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Depondt C, Godard P, Espel RS, Da Cruz AL, Lienard P, and Pandolfo M
- Subjects
- Cytochrome P-450 CYP2C9, Epilepsy drug therapy, Female, Genetic Association Studies, Genotype, Humans, Male, Middle Aged, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Anticonvulsants adverse effects, Aryl Hydrocarbon Hydroxylases genetics, Genetic Predisposition to Disease genetics, Phenytoin adverse effects
- 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., (© 2011 The Author(s). European Journal of Neurology © 2011 EFNS.)
- Published
- 2011
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