内皮素-1基因TaqI多态性与肝硬化门静脉高压的相关性研究

目的　研究内皮素 1(ET 1)基因TaqI多态性与肝硬化门静脉高压症的相关性 ,寻找新的门静脉高压形成的危险因素。方法　采用病例对照、聚合酶链反应 限制性片段长度多态性 (PCR RFLP)方法 ,分别对 10 6例乙型肝炎后肝硬化患者和 10 8名健康对照者ET 1基因内含子 4处TaqI多态性进行分析 ,并用放射免疫法检测外周血ET 1浓度。结果　门静脉高压症组TaqIC等位基因频率和CC +TC基因型频率明显高于正常对照组 ( 2 5 4%vs 16 7%、46 2 %vs 2 9 6 %) ,差异有显著意义( χ2 =4 2 6 ,OR =1 95P <0 0 5 )。提示ET 1基因TaqI多态性与门静脉高压症相关 ;在门静脉高压症组中CC与TC基因型者外周血ET 1浓度显著高于TT基因型者 (P <0 0 5 )。相关分析发现 ,ET 1基因TaqI多态性与外周血ET 1的浓度呈正相关。表明ET 1基因TaqI多态性影响ET 1的表达 ;应用Logistic多元回归分析门静脉高压形成的危险因素 ,发现ET 1基因TaqI多态性是门静脉高压形成的一个独立的危险因素。结论　ET 1基因TaqI多态性与肝硬化门静脉高压形成相关 ,可能是门静脉高压形成的危险因素之一。

Correlation between polymorphism of TaqI of ET-1 gene and cirrhotic portal hypertension

OBJECTIVE: To investigate the correlation between polymorphism of TaqI of endothelin (ET)-1 gene intron 4 and cirrhotic portal hypertension and to search new risk factor of portal hypertension. METHODS: Peripheral venous blood was extracted from 106 patients with cirrhosis after hepatitis B (PH+ group) and 108 healthy blood donors (PH- group). PCR-RFLP was used to analyze the polymorphism of TaqI of ET-1 gene. The plasma ET-1 concentration was detected with immunoassay. Multivariate logistic regression analysis was made to analyze the risk factors. RESULTS: The C allele frequency in the PH+ group was 25.4%, significantly higher than that of the controls (16.7%, P < 0.05). The frequency of CC + TC genotype in PH+ group was 46.2%, significantly lower than that in the controls (29.6%, P < 0.05). In the PH+ group, the thickness of spleen was greater, hemorrhage rate was higher, and III degrees ascites was more in C allele carrier than in T allele carriers (P < 0.05). The plasma ET-1 concentration was higher in PH+ group than in PH- group. In the PH+ group, the plasma ET-1 concentrations in those with CC genotype and those with TC genotype were significantly higher than in those with TT genotype (P < 0.05). Correlation analysis showed that ET-1 gene polymorphism was positively correlated with plasma ET-1 concentration (R = 0.808 2). Multivariate logistic regression analysis showed that gradation of liver function, diameter of portal vein, and ET-1 gene polymorphism were independent risk factors of portal hypertension. CONCLUSION: Polymorphism of TaqI of ET-1 gene is correlated with the pathogenesis of cirrhotic portal hypertension. It may be one of the risk factors of portal hypertension.