Association of ABCB1 polymorphisms with carbamazepine metabolism and resistance in epilepsy: A meta-analysis.

Abstract Objective ABCB1 polymorphisms were previously demonstrated to be associated with the metabolism and resistance of carbamazepine (CBZ) in epilepsy, but the results still remained controversial. Therefore, we performed this meta-analysis to further evaluate the impacts of ABCB1 polymorphisms on CBZ metabolism and resistance. Methods The PubMed, EMBASE, Cochrane library, Chinese National Knowledge Infrastructure, Chinese Science and Technique Journals Database and Wan Fang Database were searched for eligible publications up to 5 July 2021. The mean difference (MD), Odds ratio (OR) and 95 % confidence interval (CI) were calculated by Review Manager 5.3 software to assess the strength of the association. Results Twelve studies involving 2126 epilepsy patients were included in this meta-analysis. We found that the TC genotype (heterozygous model: TC vs. CC) of rs1045642 polymorphism was significantly connected with decreased CBZ concentration. Furthermore, this polymorphism was indicated to be associated with concentrations of carbamazepine-10, 11-epoxide (homozygote model: TT vs. CC; heterozygous model: TC vs CC; dominant model: TT + TC vs. CC; over-dominant model: TC vs. TT + CC) and carbamazepine-10, 11-trans dihydrodiol (heterozygous model: TC vs. CC; dominant model: TT + TC vs. CC). Moreover, the AG genotype of rs2032582 polymorphism was related to increased CBZ concentration in heterozygous (AG vs. GG), dominant (AA + AG vs. GG) and over-dominant (AG vs. AA + GG) models. Additionally, rs1128503 was associated with CBZ resistance in heterozygous model (TC vs. CC). Conclusions ABCB1 rs1045642 and rs2032582 polymorphisms were associated with CBZ metabolism for epilepsy, and rs1128503 was related to CBZ resistance. These findings would contribute to improving individualized therapy of epileptic patients.