GENETIC INFLUENCE OF CYP3A4 (rs2740574) GENE POLYMORPHISM ON CARBAMAZEPINE PHARMACOKINETICS IN EPILEPSY PATIENTS FROM KHYBER PAKHTUNKHWA: A PROSPECTIVE STUDY

Abstract

Objectives: This study examines CYP3A genotypes regulating CYP enzymes, specifically CYP3A4 rs2740574, in Pashtun epilepsy patients in Khyber Pakhtunkhwa, Pakistan. This study documents the pharmacogenomic effects of this single nucleotide polymorphism on carbamazepine serum levels and dose-adjusted levels. It aims to promote customized medicine by providing insights that could lead to more effective epilepsy treatments for this population.

Methods: CYP3A4 (rs2740574) genotyping was performed on 223 patients using Sanger sequencing. DNA extraction was done by salting out method manually. In subsequent follow ups serum for separated for the detection of serum levels of Carbamazepine through HPLC. Finch TV identified gene polymorphisms, and HPLC examined their effects on plasma CBZ levels.

Results: Both TC (CYP3A4 *1A/*1B) and TT (CYP3A4*1B) genotypes had higher mean doses from the first to the second follow-up, with no statistically significant difference. Carbamazepine  plasma levels increased  by 0.70 ± 2.55 mg/L and  CDR decreased by 0.41 mg/L per mg/kg/day among TT genotype carriers in the 2^nd follow up. TT & CT were 96.4% & 3.6% whereas wild CC (CYP3A4 *1A/*1A) genotype was not encountered in the study sample.

Conclusion: Genotypes of the selected gene revealed a statistically insignificant correlation with Carbamazepine pharmacokinetics.