血管紧张素转换酶及血管紧张素Ⅱ1型受体基因多态性与乙型肝炎肝硬化的关系

Relationship between genetic polymorphism in angiotensin-converting enzyme,angiotensin Ⅱ type 1 receptor and hepatitis B-related liver cirrhosis

目的研究血管紧张素转换酶(angiotensin-converting enzyme,ACE)及血管紧张素Ⅱ1型受体(angiotensinⅡtype 1 receptor,AT1R)基因多态性与乙型肝炎肝硬化之间的关联及其在乙型肝炎肝硬化的发生、发展中的作用。方法采用聚合酶链反应(polymerase chain reaction,PCR)及限制性片段长度多态性分析(restrictionfragment length polymorphism,RFLP)检测技术,对115例乙型肝炎肝硬化患者和136例正常人群中的ACE(第16个intron I/D基因)AT1R(3-′U TR 1166A/C)的基因多态性分布进行了检测。结果在ACE intron I/D基因多态性中各基因型在乙型肝炎肝硬化患者与正常人群中的差异无统计学意义(P>0.05);在乙型肝炎肝硬化患者中ACEI/D基因型的分布在有无腹水组间的差异有统计学意义,有腹水组ACE D/D基因型的频率高于无腹水组(27.8%vs11.6%,P<0.05),两组ACE的D基因频率分布差异有统计学意义(47.2%vs 31.4%,P<0.05);在乙型肝炎肝硬化患者中随着Child-Pauph分级的增高D/D基因型的比例逐渐增大(P<0.05);A、B、C 3级中D基因频率分布差异有统计学意义(P<0.05)。AT1R 1166A/C基因多态性在乙型肝炎肝硬化患者和正常人群中的差异无统计学意义(P>0.05)。结论ACE的intron D/D基因型对于乙型肝炎肝硬化是不利因素,它可能与肝硬化患者腹水的形成相关,并可促进肝硬化的进展;而AT1R的1166A/C基因位点的变异尚未显示其与肝硬化有关。

Objective To investigate the relationship between genetic polymorphism in angiotensin-converting enzyme（ACE）, angiotensin Ⅱ type 1 receptor （AT1R） and hepatitis B-related liver cirrhosis （HBV-related liver cirrhosis）. Methods Genetic polymorphisms in angiotensin-converting enzyme（NO. 16 intron I/D） and angiotensin Ⅱ type 1 receptor（3＇-UTR 1166A/C） were determined in 115 patients with HBV-related liver cirrhosis and 136 healthy blood donors by polymerase chain reaction（PCR） and restriction fragment length polymorphism（RFLP）. Results There was no significant difference in genotype distribution at NO. 16 intron I/D of ACE between two groups（ P 0.05）. While among the patients with liver cirrhosis, the genotype distribution of ACE-intron-D/D was higher in the patients with ascites than that without ascites（27.8% vs 11.6%, P〈0.05）, and the frequency of the D allele had statistically significant difference（47.2 % vs 31.4%, P〈0.05）. The genotype distribution of ACE-intron-D/D was higher in Child C group than in Child A and B group（ P〈0.05）,and the frequency of the D allele had statistically significant difference（ P〈0.05）. No significant association between 1166A/C polymorphism of AT1R gene and liver cirrhosis was confirmed （ P d0.05）. Conclusion ACE gene polymorphism appears to be associated with HBV-related liver cirrhosis,ACE intron D/D mutation may be prone to develop ascites,and ACE intron D/D genotype may play an essential role in the development and progression of hepatic fibrosis. These findings may have important therapeutic implications.