Correlation between gene polymorphism and blood concentration of calcineurin inhibitors in renal transplant recipients: An overview of systematic reviews

BACKGROUND: To provide an overview of systematic reviews and meta-analyses (SRs/MAs) of the correlation between genetic polymorphisms and blood concentrations of calcineurin inhibitors (CNIs) in recipients of renal transplant. METHODS: Databases including Medline, EMBase, The Cochrane Library (Issue 7, 2016), the Chinese Biomedical Literature Database, the China National Knowledge Infrastructure, the China Science and Technology Journal Database, and the Wan Fang Database were searched for SRs/MAs of the correlation between genetic polymorphisms and blood concentrations of CNIs in renal transplant recipients from inception to July 2016. Two reviewers independently screened the literatures and extracted data, then the AMSTAR measurement tool was used to assess the methodological quality of SRs/Mas included in the overview. RESULTS: Fourteen SRs/MAs met the inclusion criteria. The most commonly reported genotype was CYP3A5(∗)3/(∗)3, which was strongly associated with cyclosporine A (CsA) and tacrolimus (FK506). MDR1 C3435T CC was also associated with CNI use, especially with CsA therapy. Other less commonly reported genotypes such as CYP3A4(∗)1B, MDR1 C1236T CC, and MDR1 G2677T/A GG also affected the blood concentrations of CNIs. CONCLUSIONS: Our overview showed that polymorphisms influence the blood concentrations of CNIs, which suggests the necessity to monitor these concentrations in patients with genotypes that affect dose-adjusted trough concentrations (C(0)/D) or dose-adjusted peak concentrations (C(2)/D) to regulate the dosage for individual administration. Because of the limited number of included studies, these findings should be verified in more high-quality studies.