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

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.