Effect of ABCB1 3435C>T Genetic Polymorphism on Pharmacokinetic Variables of Tacrolimus in Adult Renal Transplant Recipients: A Systematic Review and Meta-analysis

Abstract

PurposeTacrolimus is the substrate of multidrug-resistance 1 (ABCB1). However, the effect of ABCB1 C3435T polymorphism on pharmacokinetic variables of tacrolimus is controversial in different studies. This meta-analysis was conducted to explore the relationship between ABCB1 3435C>T genetic polymorphism and pharmacokinetic variables of tacrolimus. MethodsA database search was conducted of PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov, as well as Chinese databases (SinoMed, Wan Fang, and China National Knowledge Infrastructure). We also scanned reference lists and corresponded with authors. The study explored the relationship between ABCB1 3435C>T genetic polymorphism and pharmacokinetic variables of tacrolimus stratified according to time of posttransplantation, ethnicity, methods of concentration measurement, and the initial doses of tacrolimus. FindingsSixteen studies were included in this meta-analysis. In the subgroup analysis, ABCB1 3435TT had a significantly lower weight-adjusted dose than ABCB1 3435CC, which was not observed in the ABCB1 3435CT group. The subgroup analysis then revealed that the tacrolimus concentration/weight-adjusted daily dose ratio of ABCB1 3435T carriers was significantly higher than that of the ABCB1 3435CC group at 1 and 6 months. Meanwhile, ABCB1 3435CT and TT both had a higher tacrolimus concentration/weight-adjusted daily dose ratio compared with ABCB1 3435CC. ImplicationsOur meta-analysis identified that the ABCB1 3435C>T genetic polymorphism affected the pharmacokinetic variables of tacrolimus in adult renal transplant recipients. However, individualized treatments based on genetic polymorphisms require further investigation.