韩国肾移植受者中常见2型糖尿病风险基因变异与移植后糖尿病的关联。

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

作者信息

Kang Eun Seok, Kim Myoung Soo, Kim Chul Hoon, Nam Chung Mo, Han Seung Jin, Hur Kyu Yeon, Ahn Chul Woo, Cha Bong Soo, Kim Soon Il, Lee Hyun Chul, Kim Yu Seun

机构信息

Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.

出版信息

Transplantation. 2009 Sep 15;88(5):693-8. doi: 10.1097/TP.0b013e3181b29c41.

DOI:10.1097/TP.0b013e3181b29c41

PMID:19741467

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.

摘要

背景

移植后糖尿病（PTDM）是肾移植受者的一种主要代谢并发症。近期全基因组关联研究已鉴定出多个与2型糖尿病相关的基因。在此，我们在韩国一组肾移植受者中检测了PTDM与位于15个基因内的17个单核苷酸多态性（SNP）之间的关联。

材料与方法

本研究纳入了1989年至2007年间接受肾移植、无糖尿病病史且移植前空腹血糖低于5.5 mmol/L的589例患者。我们分析了PTDM发生与以下SNP之间的关联：TCF7L2 rs7903146、SLC30A8 rs13266634、HHEX（rs1111875、rs7923837和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和KCNQ1 rs2237892。

结果

六个基因中的八个SNP与PTDM发生显著相关：TCF7L2 rs7903146（优势比[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）和KCNQ1 rs2237892（OR=1.46，P =0.009）。