CYP3A4 genetic polymorphisms predict cyclosporine-related clinical events in Chinese renal transplant recipients.
- Author:
Yu-Yuan WANG
1
;
Ming ZHANG
;
Fu-Ming LU
;
Zheng JIAO
;
Xiao-Yan QIU
Author Information
- Publication Type:Journal Article
- MeSH: ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1; genetics; Asian Continental Ancestry Group; genetics; Case-Control Studies; Cyclosporine; adverse effects; therapeutic use; Cytochrome P-450 CYP3A; genetics; Genotype; Humans; Immunosuppressive Agents; adverse effects; therapeutic use; Kidney Transplantation; Polymorphism, Genetic; genetics; Retrospective Studies
- From: Chinese Medical Journal 2012;125(23):4233-4238
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDCyclosporin 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.
METHODSA 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.
RESULTSThe patients with a CYP3A4 1G/ 1G genotype were found to have a higher incidence of acute rejection compared with those with CYP3A4 1/1.
CONCLUSIONCYP3A4 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.
