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

J Hepatol. 2013 Feb;58(2):271-7. doi: 10.1016/j.jhep.2012.09.025. Epub 2012 Oct 4.

Abstract

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. TT 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asian People / ethnology
  • Asian People / genetics*
  • China / epidemiology
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / ethnology
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Liver Transplantation*
  • Logistic Models
  • Male
  • Middle Aged
  • Models, Statistical
  • Polymorphism, Single Nucleotide / genetics*
  • Risk Factors
  • Tissue Donors*
  • Transcription Factor 7-Like 2 Protein / genetics*
  • Transplantation*

Substances

  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein