TGFβ1和AT1R基因多态性与乙肝肝硬化遗传易感性及临床表型的关联研究

The association of TGFβ1 and AT1R gene polymorphisms with hereditary susceptibility and clinical phenotype of HBV-induced liver cirrhosis

目的探讨与宿主肝纤维化及门脉高压形成相关的转化生长因子β1（transforming growth fac-tor beta1,TGFβ1）和Ⅰ型血管紧张素Ⅱ受体（angiotensinⅡ type 1 receptor,AT1R）基因多态性与乙肝肝硬化遗传易感性及临床表型的关系。方法应用PCR-RFLP对102例乙型肝炎后肝硬化患者和106名随机抽样的无亲缘关系的健康献血者分别检测TGFβ1启动子区-509C/T、AT1R1166A/C基因多态性。结果肝硬化组TGFβ1启动子区-509C/T纯合子CC的基因型频率明显高于对照组（P〈0.05）;肝硬化Child-PughC级组-509C/T位点CC基因型分布频率明显高于B级和A级组（P〈005）;AT1R1166A/C基因型和等位基因频率在对照组和肝硬化组之间差异均无统计学意义（P〉0.05）。结论TGFβ1启动子区-509C/T基因多态性与乙型肝炎后肝硬化遗传易感性有关,并与肝硬化严重程度密切相关,AT1R1166A/C基因多态性可能与乙型肝炎后肝硬化遗传易感性无关。

Objective To investigate the association of TGFβ1 and AT1R gene polymorphisms with hereditary susceptibility and clinical phenotype of HBV-induced liver cirrhosis. Methods Peripheral blood samples were collected from 102 patients with HBV-induced liver cirrhosis and 106 healthy blood donors. The polymorphisms of the promoter site -509C/T of TGFβ1 and 1166A/C of AT1R gene were determined by PCR-RFLP. Results The frequency of the homozygote CC of - 509C/T of TGFβ1 gene in the group of liver cirrhosis was higher than that the control group （ P 〈 0.05 ） ; and the frequency rate of homozygote CC was higher in group C than in group A and group B of liver cirrhosis （ P 〈 0.05）, but there was no significant difference in allele frequency among these group （P 〉 0.05）. There was no significant difference in genotypes and allele frequency of AT1R gene 1166A/C between the liver cirrhosis group and the control group （ P 〉 0.05）. Conclusion The polymorphism of the promoter site - 509C/T of TGFβ1 gene is associated with hereditary susceptibility to liver cirrhosis and severity of HBV-induced liver cirrhosis; the polymorphism of AT1R gene 1166A/C is not associated with hereditary susceptibility to HBV-induced liver cirrhosis.