Associations betweenCYP3A4, CYP3A5andSCN1APolymorphisms and Carbamazepine Metabolism in Epilepsy: A Meta-analysis

Abstract

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.

Voltage Gated Sodium Channel Genes in Epilepsy: Mutations, Functional Studies, and Treatment Dimensions

“…Functional studies ( Table 3 ) can help detect gain or loss-of-function variants that may guide drug design and understanding of the relationships between variants and drug response. An example of the impact of genetic variant on drug response was recently reported by Zhao et al ( 77 ) who examined the association between the SCN1A SNPs; rs3812718 and rs2298771 and the response to carbamazepine in a Chinese population. Resistance to drugs was observed with rs3812718 but not with rs2298771.…”