转录因子7样2（TCF7L2）基因变异与肾移植受者移植后糖尿病风险
A variant of the transcription factor 7-like 2 (TCF7L2) gene and the risk of posttransplantation diabetes mellitus in renal allograft recipients.
作者信息
Kang Eun Seok, Kim Myoung Soo, Kim Yu Seun, Hur Kyu Yeon, Han Seung Jin, Nam Chung Mo, Ahn Chul Woo, Cha Bong Soo, Kim Soon Il, Lee Hyun Chul
机构信息
Department of Internal Medicine, Yonsei University College of Medicine, 134 Shinchon-Dong Seodaemun-Gu, Seoul, 120-752, Korea.
出版信息
Diabetes Care. 2008 Jan;31(1):63-8. doi: 10.2337/dc07-1005. Epub 2007 Oct 12.
OBJECTIVE
Posttransplantation diabetes mellitus (PTDM) is a major complication associated with kidney transplantation. Defects in insulin secretion play a pivotal role in the pathogenesis of PTDM. A polymorphism in the transcription factor 7-like 2 (TCF7L2) gene was reported to be associated with type 2 diabetes and possibly associated with an insulin secretion defect. The aim of this study was to investigate the association between genetic variations in TCF7L2 and PTDM in renal allograft recipients.
RESEARCH DESIGN AND METHODS
A total of 511 unrelated renal allograft recipients without previously known diabetes were enrolled. Six single nucleotide polymorphisms (rs11196205, rs4506565, rs12243326, rs7903146, rs12255372, and rs7901695) were genotyped in the cohort, which consisted of 119 PTDM patients and 392 non-PTDM subjects. The genotyping of TCF7L2 polymorphisms was performed using real-time PCR.
RESULTS
rs4506565, rs7901695, and rs7903146 were found to be in complete linkage disequilibrium. The rs7903146 genotype distribution was CC 94.3% and CT 5.7%. The incidence of PTDM was significantly higher in patients with the CT genotype than in patients with the CC genotype (41.4 vs. 22.2%) (odds ratio 2.474 [95% CI 1.146-5.341]; P = 0.024). The effect of this genotype remains significant after adjustment for age, sex, amount of body weight gain, and type of immunosuppressant (2.655 [1.168-6.038]; P = 0.020).
CONCLUSIONS
These data suggest that the TCF7L2 rs7903146 genetic variation is associated with an increased risk of PTDM in renal allograft recipients.
目的
移植后糖尿病（PTDM）是肾移植相关的一种主要并发症。胰岛素分泌缺陷在PTDM的发病机制中起关键作用。据报道，转录因子7样2（TCF7L2）基因的多态性与2型糖尿病相关，且可能与胰岛素分泌缺陷有关。本研究旨在探讨肾移植受者中TCF7L2基因变异与PTDM之间的关联。
研究设计与方法
共纳入511名既往无糖尿病的非亲属肾移植受者。对队列中的6个单核苷酸多态性（rs11196205、rs4506565、rs12243326、rs7903146、rs12255372和rs7901695）进行基因分型，该队列包括119例PTDM患者和392例非PTDM受试者。采用实时PCR进行TCF7L2多态性的基因分型。
结果
发现rs4506565、rs7901695和rs7903146处于完全连锁不平衡状态。rs7903146的基因型分布为CC占94.3%，CT占5.7%。CT基因型患者的PTDM发病率显著高于CC基因型患者（41.4%对22.2%）（优势比2.474 [95%可信区间1.146 - 5.341]；P = 0.024）。在对年龄、性别、体重增加量和免疫抑制剂类型进行校正后，该基因型的影响仍然显著（2.655 [1.168 - 6.038]；P = 0.020）。
结论
这些数据表明，TCF7L2 rs7903146基因变异与肾移植受者发生PTDM的风险增加有关。
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