Association between donor and recipient TCF7L2 gene polymorphisms and the risk of new-onset diabetes mellitus after liver transplantation in a Han Chinese population

被引:73
作者
Ling, Qi [1 ]
Xie, Haiyang [1 ]
Lu, Di [1 ]
Wei, Xuyong [1 ]
Gao, Feng [1 ]
Zhou, Lin [1 ]
Xu, Xiao [1 ]
Zheng, Shusen [1 ]
机构
[1] Zhejiang Univ, Sch Med,Dept Surg, Affiliated Hosp 1,Div Hepatobiliary & Pancreat Su, Key Lab Combined Multiorgan Transplantat,Minist P, Hangzhou 310003, Zhejiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Liver transplantation; New-onset diabetes mellitus; TCF7L2; polymorphism; GENOME-WIDE ASSOCIATION; RENAL-ALLOGRAFT RECIPIENTS; LONG-TERM OUTCOMES; 7-LIKE; TCF7L2; IMPACT; VARIANTS; LOCI;
D O I
10.1016/j.jhep.2012.09.025
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Backgrounds & Aims: New-onset diabetes mellitus (NODM) is a frequent and serious complication arising after liver transplantation (LT). Transcription factor 7-like 2 (TCF7L2) polymorphisms have been reported to strongly associate with type 2 diabetes. In addition, the donor liver plays a vital role in regulating blood glucose levels. In this study, we aim at evaluating the association between donor and recipient TCF7L2 gene polymorphisms with NODM after LT. Methods: A total of 125 patients undergoing primary LT, without a history of diabetes were included. Four single nucleotide polymorphisms (rs290487, rs7903146, rs11196205, and rs12255372), closely associated with type 2 diabetes in the Eastern Asia population, were genotyped and analyzed. Results: Both donor and recipient rs290487 polymorphisms (CC vs. IT genotype) were found to be significantly associated with NODM. In multivariate analysis, donor rs290487 genetic variation (OR = 2.172 per each C allele, p = 0.015), blood tacrolimus levels at 1 month post-LT >10 ng/ml (OR = 3.264, p = 0.017), and recipient age >55 years (OR = 2.638, p = 0.043) were identified as independent risk factors of NODM. Furthermore, donor rs290487 CC genotype could predict a high probability (>40%) of the onset of NODM. Predictive model containing donor rs290487 polymorphism showed a significantly higher prognostic ability on NODM than the model with only clinical parameters (p = 0.031). Conclusions: Donor TCF7L2 rs290487 polymorphism is associated with an increased risk of NODM after LT and has a potential clinical value for the prediction of NODM. (C) 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:271 / 277
页数:7
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