TGF-β1基因多态性与乙型肝炎肝硬化的相关性研究

摘要

Objective To investigate the association between transforming growth factor betal ( TCF - β1) gene polymorphism and liver cirrhosis with chronic HBV infection in Chinese Han population. Methods Blood samples were obtained from 173 HBV infectors in Chinese Han population ( including 131 non - hepatocirrhosis cases and 42 hepatocirrhosis cases) and 52 healthy controls. The 4 varianees of TGF - β1 genes ( TGF - β1, 869T/C ,915G/C , - 800 G/A , - 509 C/T) were identified by DNA sequencing, while TCF - β1 level in serum was also measured by ELISA. Results (1)The frequency of TGF - β1 869TT genotype in chronic HBV hepatocirrhosis patients ( 47 . 6％ ) was higher than that in non - hepatocirrhosis cases( 25 . 2％ ) and controls ( 19. 2％) significantly , respectively. The allele frequency of TGF - β1 869T in hepatocirrhosis patients ( 63. 1％ ) was significant higher than that in controls ( 44. 2％ ) ( P ＜ 0. 05).( 2) There was no significant difference within groups relating to the other gene - loci of TGF - β1 ( P ＞0. 05 ) . ( 3)In the test of TGF - β1 serum level within 869T/C different genotype, it was found that serum level of TGF - β1, in T/T was increased comparing to T/C and C/ C genotypes, and the difference was statisiically significant( P ＜ 0. 017). Conclusion There may be an association between TGF - β1 869T and Chineae Han inherited susceptibility of liver fibrosis in chronic HBV infectors, which influences the serum level of TGF - β1 probably, then participates in the development of liver fibrosis.%目的 探讨转化生长因子-β1 (TGF-β1)基因多态性是否与慢性HBV感染人群肝硬化发生的遗传易感相关.方法 收集173例中国汉族慢性HBV感染患者(肝硬化组42例和非肝硬化组131例)和52例健康对照者的外周血标本,提取白细胞DNA,基因直接测序法检测TGF-β1基因4个多态性(869T/C、915G/C、-800 G/A、-509 C/T),ELISA法检测TGF-β1血清浓度,比较各组TGF-β1基因型分布频率、等位基因频率及TGF-β1血清水平的差异.结果 (1)乙型肝炎肝硬化组TGF-β1 869位点以TT基因型为主(47.6%),高于非肝硬化组(25.2%)和对照组(19.2%),差异有统计学意义(P<0.05);869T等位基因频率(63.1%)明显高于正常对照组(44.2%),差异有统计学意义(P<0.05),乙型肝炎肝硬化组与慢性HBV感染非肝硬化组(53.8%)、慢性HBV感染非肝硬化组与正常组869T等位基因携带率相比,差异无统计学意义(P>0.05).(2)所检其余多态性位点基因型及基因频率未见组间统计学差异.(3)869T/C不同基因型患者的血清TGF-β1水平不一,T/T型携带者较T/C和C/C型可见明显增高(P<0.017).结论 TGF-β1 869T可能与汉族人群乙型肝炎肝硬化的遗传易感相关,其机制可能与该多态性对TGF-β1血清水平的影响有关.