Qi Ling1, Haiyang Xie, Di Lu, Xuyong Wei, Feng Gao, Lin Zhou, Xiao Xu, Shusen Zheng. 1. Key Lab of Combined Multi-Organ Transplantation, Ministry of Public Health, Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
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.
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, donorrs290487 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, donorrs290487 CC genotype could predict a high probability (>40%) of the onset of NODM. Predictive model containing donorrs290487 polymorphism showed a significantly higher prognostic ability on NODM than the model with only clinical parameters (p = 0.031). CONCLUSIONS:DonorTCF7L2rs290487 polymorphism is associated with an increased risk of NODM after LT and has a potential clinical value for the prediction of NODM.
Authors: Miguel Jiménez-Pérez; Rocío González-Grande; Edith Omonte Guzmán; Víctor Amo Trillo; Juan Miguel Rodrigo López Journal: World J Gastroenterol Date: 2016-07-28 Impact factor: 5.742