The effect of CYP3A5 polymorphism on dose-adjusted cyclosporine concentration in renal transplant re

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  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.Twelve and 6 studies meeting the inclusion criteria were respectively included in meta-analysis about dose-adjusted trough concentration (C0/D) and dose-adjusted peak concentration (C2/D).The combined weighted mean difference (WMD) between CYP3A5 expressers (*1/*3 + *1/*1) and non-expressers (*3/*3) was significant in C2/D [WMD =-12.73 (ng/ml)/(mg/kg), 95% confidence interval (CI):-25.23--0.22, P =0.046], while it was marginally significant in C0/D [WMD =-3.75 (ng/ml)/(mg/kg), 95% CI:-7.58-0.07, P =0.054].Exclusion of an outlier study greatly increased the association of CYP3A5 polymorphism with C0/D to be significant [WMD =-4.92 (ng/ml)/(mg/kg), 95% CI:-8.27--1.58, P =0.011].This meta-analysis showed 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.
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