内皮素-1基因TaqⅠ和肿瘤坏死因子α基因多态性与肝硬化门静脉高压的相关性

目的 探讨内皮素-1基因Taq Ⅰ多态性和肿瘤坏死因子(TNF)α基因多态性与肝硬化门静脉高压之间的相互关系。 方法 采用病例对照和聚合酶链反应-限制性片段长度多态性等技术,检测了106例乙型肝炎后肝硬化患者和108名健康对照者内皮素～1基因Taq Ⅰ多态性和TNF α基因启动子-308G→A多态性,比较等位基因及基因型频率,并进行分层分析。 结果 在ET—1基因Taq Ⅰ多态性中,门静脉高压症组(LC )C等位基因频率和CC TC基因型频率分别为25.38％与46.15％,比正常对照组明显升高(16.67％与30.56％,x2=4.26,P<0.05)。在TNF α基因多态性中,LC 组TNF2/1基因型的频率比对照组明显升高(21.54％对10.19％,P<0.05)。分层分析发现由这两个基因多态性组成的不同基因型中,TCF 2基因型频率在LC 组高于正常对照组(P<0.05,OR=2.03)。Logistic多元逻辐回归分析显示,ET-1和TNFα基因多态性是门静脉高压形成的危险因子(P值分别为0.022和0.043)。 结论 ET—1和TNF α基因多态性与肝硬化门静脉高压症相关,是门静脉高压症形成的新的危险因子。TCF2基因型可能是门静脉高压症的易感基因型。

Relationship of endothelin-1 (ET-1) TaqⅠ and tumor necrosis factor (TNF) α gene polymorphism with portal hypertension in liver cirrhosis

OBJECTIVE: To study whether liver cirrhosis and portal hypertension are associated with ET-1 TaqI polymorphism and TNFa promoter-308G to A polymorphism. METHODS: A case control study of 106 patients with liver cirrhosis following HBV C infection was performed in comparison with 108 controls by PCR-RFLP. RESULTS: The frequency of C allele and CC+TC genotype in TaqI polymorphism of ET-1 gene in the portal hypertension group (LC+) was significantly higher than that in the healthy controls, and the frequency of TNF2/1 genotype in TNFa promoter -308 G to A polymorphism in LC+ group was significantly higher than that in the control group. The results by stratification analysis showed that TCF2 genotype frequency was higher in the LC+ group than in the control group. ET-1 TaqI polymorphism and TNFa polymorphism were risk factors for the occurrence of portal hypertension by Logistic regression analysis. CONCLUSION: ET-1 TaqI polymorphism and TNFa polymorphism are associated with portal hypertension, and are new risk factors for the occurrence of portal hypertension. TCF2 genotype may be a susceptible gene of portal hypertension.