The effect of CYP3A5 polymorphism on dose-adjusted cyclosporine concentration in renal transplant recipients: a meta-analysis.

Cyclosporine (CsA) is a substrate of cytochrome P450 (CYP) 3A5 and has a narrow therapeutic range with large inter-individual variability. CYP3A5*3 polymorphism is reported to be functional and may contribute to the inter-individual variability. The objective of this meta-analysis was to accurately estimate the effect of CYP3A5*3 allele on CsA dose-adjusted blood concentration. A computerized literature search was conducted in PubMed. A total of 12 and 6 studies meeting the inclusion criteria were, respectively, included in meta-analysis about dose-adjusted trough concentration (C(0)/D) and dose-adjusted peak concentration (C(2)/D). The combined weighted mean difference (WMD) between CYP3A5 expressers (*1/*3 + *1/*1) and non-expressers (*3/*3) was significant in C(2)/D (WMD = -12.73 (ng ml(-1))/(mg kg(-1)), 95% confidence interval (CI) -25.23 to -0.22, P = 0.046), whereas it was marginally significant in C(0)/D (WMD = -3.75 (ng ml(-1))/(mg kg(-1)), 95% CI -7.58 to 0.07, P = 0.054). Exclusion of an outlier study greatly increased the association of CYP3A5 polymorphism with C(0)/D to be significant (WMD = -4.92 (ng ml(-1))/(mg kg(-1)), 95% CI: -8.27 to -1.58, P = 0.011). This meta-analysis showed that CYP3A5*3 polymorphism is associated with CsA dose-adjusted concentration in renal transplant recipients. Patients carrying the CYP3A5*3/*3 genotype will require a lower dose of CsA to reach target levels compared with the CYP3A5*1/*1 or *1/*3 carriers.