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.
Gene. 2013 Jun 15;522(2):214-8. doi: 10.1016/j.gene.2013.03.089. Epub 2013 Apr 2.
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.
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.
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.
TCF7L2 polymorphisms were associated with HD and maybe cancer risk as well. Further studies with large samples are needed to verify these results.
肝源性糖尿病（HD）是肝硬化的并发症之一。遗传因素是否除了肝脏损伤以外也在 HD 的发生发展中起作用尚不清楚。TCF7L2 基因已被报道与 2 型糖尿病和癌症风险相关。我们旨在评估 TCF7L2 基因在中国汉族人群中对 HD 和肝细胞癌（HCC）易感性的影响。
共纳入 367 名成年肝移植候选者，均患有肝硬化。从 HapMap CHB 数据库中选择了 15 个标签单核苷酸多态性（SNP），其等位基因频率>0.2，r(2)>0.8。另外选择了 3 个 SNP，因为它们与东亚 2 型糖尿病密切相关。
与非 HD 患者相比，HD 患者的肝功能更差，肝硬化并发症发生率更高，胰岛素抵抗更明显。3 个 SNP 在 HD 患者和非 HD 患者之间的分布存在差异。在多变量 logistic 分析中，在调整临床因素后，TCF7L2 rs290487 和 rs6585194 多态性与 HD 独立相关。与 T/T 和 T/C 基因型相比，TCF7L2 rs290487 C/C 纯合子显示出更高的胰岛素抵抗和显著增加的 HD 风险，而 rs6585194 的遗传变异对 HD 具有保护作用。位于 TCF7L2 基因 3' 末端附近的 3 个 SNP(rs290481、rs290487 和 rs290489)与 HCC 风险相关，但具有边缘显著性。携带 G-C-A 单倍型的患者 HCC 风险显著高于携带 A-T-G 单倍型的患者。
TCF7L2 多态性与 HD 相关，也可能与癌症风险相关。需要进一步进行大样本研究来验证这些结果。
