Association of calpain-10 gene polymorphism and posttransplant diabetes mellitus in kidney transplant patients medicated with tacrolimus.

Abstract

New-onset, posttransplant diabetes mellitus (PTDM) has a high incidence after kidney transplantation in patients medicated with tacrolimus, and may adversely affect the patient and graft survival. The pathophysiology of PTDM closely mimics that of type II diabetes mellitus (T2DM). One of possible genetic factors predisposing to PTDM might be polymorphism in calpain-10 gene (CAPN10), previously associated with increased risk of T2DM in general population. Therefore, the present study was aimed at evaluation of CAPN10 gene polymorphisms in PTDM in kidney transplant patients medicated with tacrolimus. A total of 214 nondiabetic kidney transplant patients medicated with tacrolimus (56 patients with PTDM and 158 patients without PTDM were genotyped for the presence of CAPN10 gene variants (SNP-43: rs3792267:G>A, SNP-19: rs3842570 ins/del and SNP-63: rs5030952:C>T) using PCR-based assays. Frequency of SNP-63 minor allele was slightly increased in PTDM patients (P=0.056), and an association of SNP-63 heterozygosity and the risk of PTDM (odds ratios (OR)=2.45, P=0.023) was observed. An increased odds for PTDM development in patients carrying 1-1-2 haplotype (rs3792267:G-rs3842570:ins-rs5030952:T) compared to noncarriers was also noted (OR=2.35, P=0.026). Patients' higher body mass index and SNP-63 minor T allele carrier status were identified as independent PTDM risk factors, confirmed by multivariate regression analysis. This is the first study of CAPN10 polymorphism in relation to PTDM risk. However, the application of SNP-63 (rs5030952:C>T) as a marker of PTDM should be verified by further independent studies.