CYP3A4 genetic polymorphisms predict cyclosporine-related clinical events in Chinese renal transplant recipients.

Background Cyclosporin A (CsA) is a substrate of both cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), some of the single nucleotide polymorphisms (SNPs) in these genes are associated with interindividual variations in CsA pharmacokinetics. We studied the influence of these SNPs on the incidence of rejection and CsA nephrotoxicity, as well as pneumonia within one year after renal transplant and post-transplantation diabetes mellitus (PTDM), in order to find whether genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes. Methods A total of 208 renal transplant recipients receiving CsA were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T), CYP3A4*1G, and CYP3A5*3 by direct sequencing method. Retrospective case control study was utilized to identify the association between CYP3A4*1G, CYP3A5*3, ABCB1 genetic polymorphisms and CsA-related outcomes. Results The patients with a CYP3A4*1G/*1G genotype were found to have a higher incidence of acute rejection compared with those with CYP3A4*1/*1. Conclusion CYP3A4*1G/*1G genotype predict increased risk of acute rejection, so genetic evaluation may partly help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes. Chin Med J 2012;125(23):4233-4238