CYP3A5 genetic variants and their associations with carbamazepine and valproic acid response in Malaysian epileptic patients

Objective: Epilepsy is a common chronic neurological condition characterized by recurrent seizures. Approximately 30 - 40% of epileptic patients do not respond to antiepileptic drugs. Previous studies suggest that CYP3A5 polymorphisms affect carbamazepine metabolism. Materials and methods: To examine this hypothesis, in the present study, the associations between CYP3A5 variants (rs776746 and rs1419745) and response to carbamazepine and valproic acid monotherapy in Malaysian epileptic patients were evaluated. Results: A total of 288 Malaysian epileptic patients were recruited and further reviewed, of whom 63 patients were on carbamazepine monotherapy, and 85 patients were on valproic acid monotherapy. There was no patient with drug hypersensitivity syndrome within the population. Subjects were genotyped by using Sequenom MassARRAY platform. This study found a significant association of CYP3A5 rs776746 with the carbamazepine treatment response in total patients (p = 0.026) and Malay ethnic subgroup (p = 0.006). In addition, a marginal significant association of CYP3A5 rs1419745 with carbainampine treatment response was reported in the Malays. Similarly. CYP3A5 rs776746 was associated with valproic acid response in total patients (p = 0.037) and Malays (marginal p = 0.05). Conclusion: Our findings suggest that CYP3A5 polymorphisms affect carbamazepine and valproic acid response in Malaysian epileptic patients.