Impact of CYP2C9*2 and *3 polymorphisms on valproate-associated adverse drug reactions in individuals living with epilepsy: a case–control study

Abstract

Epilepsy is characterized by repeated seizure activity. Valproate, a commonly used antiepileptic drug, shows large inter-individual variation in plasma valproic levels and causes many adverse drug reactions. Aim: To find the influence of CYP2C9*2 and *3 polymorphisms on valproate-associated adverse drug reactions and plasma valproic acid levels in people with epilepsy. Methods: We recruited 158 people with epilepsy (79 cases and 79 controls) from an epilepsy clinic. Steady-state plasma valproic acid levels were measured using liquid chromatography-mass spectrometry and genotyping of CYP2C9 variants was carried out with helps of RT-PCR. Results: The presence of a mutant heterozygous genotype showed an odds ratio (OR) of 2.82 (95% CI: 1.10–7.24) and the adjusted OR was 5.39 (95% CI: 1.69–17.16). There was no significant difference in steady-state plasma valproate concentration between genotypes. Conclusion: The presence of a mutant heterozygous CYP2C9 genotype possesses five-times the risk of developing adverse drug reactions to valproate in people with epilepsy.