Association between the CYP3A4 *18B polymorphism and pharmacokinetics of cyclosporine-A in recipients of kidney transplantation in Chinese patients: a meta-analysis of observational studies

Purpose: The mutation frequency of the CYP3A4 *18B genetic polymorphism is relatively high in Asian populations. The influence of this polymorphism on the pharmacokinetics of cyclosporine A (CsA) is controversial. We investigated the association between the CYP3A4 *18B polymorphism and CsA pharmacokinetics in Chinese renaltransplant recipients. Methods: A literature search was conducted in PubMed, the Cochrane Library, EMBASE and the Chinese Wanfang database. Three studies involving 232 recipients were studied. Results: Our results showed a significant difference in the mean CsA dose-adjusted peak concentration (C2) between carriers of CYP3A4 *1/*1 and carriers of CYP3A4 *18B (standard mean difference (SMD), 0.26; 95% confidence interval (95% CI), 0.08-0.44; P=0.005). Compared with subjects with CYP3A4 *1/*18B (AG)-CYP3A5 *1/*3 (AG) or CYP3A4 *18B/*18B (AA)CYP3A5 *1/*1 (AA), a significantly higher CsA dose-adjusted C2 was required in recipients with CYP3A4 *1/*1 (GG) -CYP3A5 *3/*3 (GG) when pooled data were evaluated regardless of post-transplant time points (SMD, 0.22; 95% CI, 0.03-0.42; P=0.027). Conclusions: These findings suggest that, relative to carriers of CYP3A4 *18B, recipients with CYP3A4 *1/*1 (especially those carrying CYP3A4 *1/*1 and CYP3A5 *3/*3) require a lower maintenance dose to achieve target CsA concentrations in blood 1 month after transplantation.