The Impact of ABCB1 SNPs on Tacrolimus Pharmacokinetics in Liver or Kidney Transplant Recipients: A Meta-analysis

Abstract

Purpose: We aimed to investigate the association between ATP Binding Cassette Subfamily B Member 1 (ABCB1) single nucleotide polymorphisms (SNPs) and the pharmacokinetics of tacrolimus. Methods: A systematic search was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase from inception to November 2022. Outcomes included weight-adjusted daily dose (DD) and dose-adjusted trough concentration (C0/Dose). Results: A total of 1059 liver or kidney transplant recipients from 14 publications were included. For adult liver transplantation recipients, DD of ABCB1 3435C>T CC carriers was 0.03 mg/kg/day (WMD = 0.03, 95% CI: 0.01 to 0.05, I 2 = 0%) higher than ABCB1 3435C>T T carriers at post-transplantation ≤ 7 days; C0/dose of ABCB1 3435C>T CC carriers were 31.88 (WMD = -31.88, 95% CI: -62.32 to -1.45, I 2 = 83.5%) or 34.61 (ng/ml)/(mg/kg/day) (WMD = -34.61, 95% CI: -65.26 to -3.97, I 2 = 55.3%) lower than ABCB1 3435C>T T carriers at post-transplantation ≤ 7 or 14 days, respectively. No difference in C0/dose was observed for ABCB1 2677G>T/A or ABCB1 1236C>T SNPs in both liver and kidney transplant recipients. Conclusion: ABCB1 3435C>T SNP might have a potential impact on tacrolimus pharmacokinetics in the early stage after liver transplantation, indicating the probability of individualized immunosuppressive therapy based on genetic polymorphism. Given some limitations, further well-designed prospective studies are warranted to validate these conclusions.

Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies

“…A few meta-analyses had shown an association between genetic polymorphisms of cytochrome P450 (CYP) or the ATP Binding Cassette Subfamily B Member 1 (ABCB1) and the pharmacokinetics of tacrolimus in the renal transplant recipients. For example, tacrolimus trough blood concentration/Dose (C 0 /Dose) ratio was significantly lower in CYP3A5*1, CYP3A4*1B or *1G, or ABCB1 3435CC carriers than CYP3A5*3/*3, CYP3A4*1/*1, or ABCB1 3435 T carriers, and CYP3A4*1/*1 or ABCB1 3435TT carriers required a lower weight-adjusted tacrolimus daily dose compared to CYP3A4*1B or *1G, or ABCB1 3435CC carriers [ 8 – 12 ]. However, the selection of the optimal initial dose and dose adjustment based on the genetic background were still not widely performed in clinical practice due to insufficient clinical evidence [ 13 ].…”