Associations between CYP3A4, CYP3A5 and SCN1A Polymorphisms and Carbamazepine Metabolism in Epilepsy: A Meta-analysis

Background and objective: CYP3A4 (rs2242480), CYP3A5 (rs776746) and SCN1A (rs3812718 and rs2298771) gene polymorphisms were previously indicated to be associated with carbamazepine (CBZ) metabolism and resistance in epilepsy. However, previous studies regarding the effects of these polymorphisms still remain controversial. Therefore, we performed a meta-analysis to evaluate whether the four polymorphisms are associated with CBZ metabolism and resistance. Methods: The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database, China Biology Medicine disc and Wan fang Database were searched up to January 2020 for appropriate studies regarding the association of rs2242480, rs776746, rs3812718 and rs2234922 polymorphisms with metabolism and resistance to CBZ. The meta-analysis was conducted by Review Manager 5.3 software. Results: Eighteen studies involving 2574 related epilepsy patients were included. Significant associations between CYP3A4 rs2242480, CYP3A5 rs776746 and SCN1A rs3812718 polymorphisms and plasma concentrations of CBZ were observed. Additionally, SCN1A rs3812718 polymorphism was significantly associated with CBZ resistance. However, no association was observed between SCN1A rs2298771 polymorphism and metabolism and resistance to CBZ. Conclusion: The CYP3A4 rs2242480, CYP3A5 rs776746 and SCN1A rs3812718 polymorphisms may play important roles in metabolism and resistance to CBZ, while SCN1A rs2298771 polymorphism is not associated with CBZ in epilepsy. These findings would improve the individualized therapy of epileptic patients in clinics.