Effects of EPHX1 and CYP3A4*22 genetic polymorphisms on carbamazepine metabolism and drug response among Tunisian epileptic patients

Abstract

The aim of this study was to evaluate the impact of polymorphisms in the EPHX1 (c.416A > G, c.337T > C) and CYP3A4*22 genes involved in carbamazepine (CBZ) metabolism and pharmacoresistance among 118 Tunisian patients with epilepsy under maintenance dose of CBZ. These genetic polymorphisms were analyzed by PCR-RFLP. Associations between plasma CBZ concentration, CBZ-E concentration, maintenance doses and metabolic ratio (CBZ-E:CBZ, CBZ-D:CBZ-E) were analyzed with each polymorphism. Both variants of EPHX1 c.416A > G and c.337T > C are significantly associated with higher metabolic ratio CBZ-E:CBZ and seem to decrease the activity of the epoxide hydrolase. The CYP3A4*22 variant allele is significantly associated with lower CBZ-D:CBZ-E ratio and seems also to be associated with less activity of the cytochrome. Our data suggest that certain polymorphisms of metabolizing enzyme genes could influence inter-individual variability of CBZ metabolism.

Keywords:

• CYP3A4*22
• drug metabolism
• EPHX1 gene

Acknowledgements

This study was supported by the ‘‘Higher Education and Scientific Research Ministry’’ in Tunisia. We thank all the staff of the Laboratory of Metabolic Biophysics, Professional Toxicology and Applied Environmental Laboratory (LR12ES02), Medicine Faculty of Sousse, Tunisia for their help and assistance.

Disclosure statement

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the manuscript.