Effects of CYP3A4*22 polymorphism on trough concentration of tacrolimus in kidney transplantation: a systematic review and meta-analysis.

Tacrolimus (Tac) is a widely used immunosuppressive agent in kidney transplantation. Cytochrome P450 (CYP), especially enzymes are responsible for the metabolism of drugs. However, the correlation between plasma Tac concentration and gene variants is controversial. This meta-analysis aims to evaluate the association between polymorphism and the dose-adjusted trough concentration (C/D) of Tac in adult kidney transplant patients. We conducted a literature review for qualifying studies using the PubMed, Web of Science, and Embase databases until July 2023. For the continuous variables (C/D and daily dose), mean difference (MD) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between the and Tac pharmacokinetics. We performed an additional analysis on the relationship of with Tac PKs and analyzed the effects of in CYP3A5 non-expressers. Overall, eight eligible studies with 2,683 renal transplant recipients were included in this meta-analysis. The allele was significantly associated with a higher C/D (MD 0.57 ng/mL/mg (95% CI: 0.28 to 0.86; = 0.0001) and lower mean daily dose requirement (MD -2.02 mg/day, 95% CI: -2.55 to -1.50; < 0.00001). An additional meta-analysis demonstrated that carrying the polymorphism greatly impacted Tac blood concentration. From the result with CYP3A5 non-expressers, showed significant effects on the Tac C/D and dose requirement even after adjusting the effect of . Patients with allele showed significantly higher plasma C/D of Tac and required lower daily dose to achieve the therapeutic trough level after kidney transplantation. These findings of our meta-analysis may provide further evidence for the effects of genetic polymorphism in on the PKs of Tac, which will improve individualized treatment in a clinical setting.