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

• Published in: International journal of clinical pharmacology and therapeutics Vol. 59; no. 1; pp. 8 - 16
• Main Authors: Miyata-Nozaka, Yuka, Tan, Hui Jan, Wong, Sau Wei, Raymond, Azman Ali, Omar, Haslyna, Zain, Shamsul Mohd
• Format: Journal Article
• Language: English
• Published: Germany Dustri - Verlag Dr. Karl Feistle GmbH & Co. KG 01.01.2021
• Subjects: Acids; Anticonvulsants - adverse effects; Antidepressants; Carbamazepine - therapeutic use; Cluster analysis; Convulsions & seizures; Cytochrome P-450 CYP3A - genetics; Enzymes; Epilepsy; Epilepsy - drug therapy; Epilepsy - genetics; Equilibrium; Genotype & phenotype; Humans; Malaysia; Medicine; Patients; Software; Substance abuse treatment; Valproic Acid - adverse effects; Malaysia
• ISSN: 0946-1965
• DOI: 10.5414/CP203761

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 polymorphisms affect carbamazepine metabolism. To examine this hypothesis, in the present study, the associations between variants (rs776746 and rs1419745) and response to carbamazepine and valproic acid monotherapy in Malaysian epileptic patients were evaluated. 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 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 rs1419745 with carbamazepine treatment response was reported in the Malays. Similarly, rs776746 was associated with valproic acid response in total patients (p = 0.037) and Malays (marginal p = 0.05). Our findings suggest that polymorphisms affect carbamazepine and valproic acid response in Malaysian epileptic patients.