title: Impacts of TCF7L2 gene polymorphisms on the susceptibility of hepatogenous diabetes and hepatocellular carcinoma in cirrhotic patients.
abstract: BACKGROUND
  Hepatogenous diabetes (HD) occurs as a complication of cirrhosis. Whether genetic factors, rather than only liver damage, play roles in the development of HD is unknown. TCF7L2 gene has been reported to be associated with type 2 diabetes and also cancer risks. We aim to evaluate the impact of TCF7L2 gene on the susceptibility of HD and hepatocellular carcinoma (HCC) in a Chinese Han population.
  
  
  METHODS
  A total of 367 adult liver transplant candidates with liver cirrhosis were included. Fifteen tag single nucleotide polymorphisms (SNPs) were selected from HapMap CHB database with a minor allele frequency of >0.2 and r(2) of >0.8. Another three SNPs were also chosen because of their close association with type 2 diabetes in East Asian.
  
  
  RESULTS
  Patients with HD presented significantly poorer liver function, higher incidence of cirrhotic complications and higher insulin resistance compared with non-HD patients. Three SNPs were differentially distributed between HD patients and non-HD patients. In multivariate logistic analysis, TCF7L2 rs290487 and rs6585194 polymorphisms were independently associated with HD after adjustment of clinical factors. The TCF7L2 rs290487 C/C variant homozygote showed much higher insulin resistance and significantly increased HD risk comparing with T/T and T/C genotypes, while the genetic variant of rs6585194 was protectively against HD. Three SNPs (rs290481, rs290487 and rs290489) located near the 3' end of TCF7L2 gene were associated with HCC risk with marginal significance. Patients carrying G-C-A haplotype had a significantly higher HCC risk than those with A-T-G.
  
  
  CONCLUSIONS
  TCF7L2 polymorphisms were associated with HD and maybe cancer risk as well. Further studies with large samples are needed to verify these results.
authors.affiliation: 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.
authors.forename: Qi
authors.initials: Q
authors.lastname: Ling
authors.forename: Fengqin
authors.initials: F
authors.lastname: Dong
authors.forename: Lei
authors.initials: L
authors.lastname: Geng
authors.forename: Zhikun
authors.initials: Z
authors.lastname: Liu
authors.forename: Haiyang
authors.initials: H
authors.lastname: Xie
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D044466:Asian People / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002681:China; D048909:Diabetes Complications / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008103:Liver Cirrhosis / Q000209:etiology / Q000235:genetics*; D008113:Liver Neoplasms / Q000235:genetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics*
chemical_list: C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein