Association of common type 2 diabetes risk gene variants and posttransplantation diabetes mellitus in renal allograft recipients in Korea

Abstract

BACKGROUND: Posttransplantation diabetes mellitus (PTDM) is a major metabolic complication in renal transplant recipients. Recent genome-wide association studies have identified several genes associated with type 2 diabetes. Here, we examined the association between PTDM and 17 single nucleotide polymorphisms (SNPs) located within 15 genes in a cohort of renal allograft recipients in Korea.

MATERIALS AND METHODS: A total of 589 patients who received kidney transplants between 1989 and 2007, without a history of diabetes and had a pretransplant fasting glucose less than 5.5 mmol/L were included in this study. We analyzed the association between the PTDM development and the following SNPs: TCF7L2 rs7903146, SLC30A8 rs13266634, HHEX (rs1111875, rs7923837, and rs5015480), CDKAL1 rs10946398, CDKN2A/B rs10811661, IGF2BP2 rs4402960, FTO rs8050136, WFS1 rs734312, JAZF1 rs864745, CDC123/CAMK1D rs12779790, TSPAN8 rs7961581, THADA rs7578597, ADAMTS9 rs4607103, NOTCH2 rs1092391, and KCNQ1 rs2237892.

RESULTS: Eight SNPs in six genes were significantly associated with the PTDM development: TCF7L2 rs7903146 (odds ratio [OR]=2.20, P =0.016), SLC30A8 rs13266634 (OR=1.52, P =0.003), HHEX rs1111875 (OR=1.47, P =0.007), HHEX rs7923837 (OR=2.32, P =0.014), HHEX rs5015480 (OR=1.59, P =0.003), CDKAL1 rs10946398 (OR=1.43, P =0.008), CDKN2A/B rs10811661 (OR=1.33, P =0.039), and KCNQ1 rs2237892 (OR=1.46, P =0.009).

CONCLUSIONS: These data suggest that genetic variations in TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, and KCNQ1 are associated with PTDM in Korea.