Influence of EPHX1 c.337T>C and UGT2B7*2 genetic polymorphisms on the requirement of carbamazepine maintenance dose in persons with epilepsy (PWE) of Southern part of India: a cross-sectional genetic association study.

Abstract

Carbamazepine (CBZ) is a first-line antiseizure drug used for focal onset seizures. It exhibits inter-individual variability in plasma carbamazepine levels and there are both genetic and non-genetic factors having arole in the requirement of CBZ maintenance dose. The aim was to study the influence of EPHX1 c.337T>C and UGT2B7*2 genetic polymorphisms on CBZ maintenance dose requirement in persons with epilepsy. Persons with epilepsy (PWE) of both gender of age 15-65 years on carbamazepine monotherapy who had been taking same maintenance dose for one year were eligible. Five milliliter of venous blood was collected in 10%EDTA under aseptic precautions. After centrifugation, the cellular component was used for DNA extraction and genotyping. For three genotypes of EPHX1 c.337T>C and UGT2B7*2, the differences in mean carbamazepine dose were analyzed using Analysis of Variance (ANOVA). An unpaired t-test was used to draw a comparison between thegenotypes and CBZ maintenance dose requirement fordominant and recessive models of EPHX1 c.337T>C andUGT2B7*2. A value of p<0.05 was considered to be statistically significant. For UGT2B7*2 (rs 7439366), CT required a higher dose (CT 626mg/day and TT 523mg/day) but not found tobesignificant (p-value 0.167). PWE carrying CT genotypeofEPHX1 c.337T>C had 62mg higher dose when compared to homozygous mutant CC (590mg/day for CT and 528mg/day for CC) but p-value was not found to be significant (p-value 0.835). The results of our study done in 115 PWE showed there was a lack of association between SNPs of EPHX1 c.337T>C, UGT2B7*2 and CBZ maintenance dose requirement in Southern part of India and this finding has tobe confirmed in a larger sample size.