TNF-α、TGF-β1和IL-10基因多态性与乙型肝炎后肝硬化的关系

Relationship between TNF-α, TGF-β1 and IL-10 genetic polymorphisms and posthepatitis B cirrhosis

目的:探讨上海人群中TNF-α、TGF-β1及IL-10单核苷酸多态性与乙型肝炎后肝硬化的关联.方法:运用PCR-RFLP结合测序的方法,测定119例健康对照者与169例肝硬化患者TNF-α基因-308G/A、TGF-β1基因-509T/C、IL-10基因-592A/C的多态性,并确定其基因型与等位基因频率的分布.结果:乙型肝炎后肝硬化患者TNF-α的GG基因型和G等位基因出现的频率明显高于健康对照者(P<0.001,OR>3);TGF-β1-509位点的3种基因型整体间没有差异,但T等位基因出现的频率明显高于健康对照者(P<0.05);IL-10-592A/C的多态性在乙型肝炎后肝硬化患者与健康对照者之间差异没有统计学意义.结论:TNF-α-308G/A与TGF-β1-509T/C的多态性可能与乙型肝炎后肝硬化的遗传易感性有关.

AIM： To investigate the relationship between single nucleotide polymorphisms （SNPs） of the tumor necrosis factor-α （TNF-α）, transforminggrowth factor-β1 （TGF-β1） and interleukin-10 （IL-10） genes and post-hepatitis B cirrhosis in the Shanghai Chinese population. METHODS： The TNF-α-308G/A, TGF-β1-509T/ C and IL-10-592A/C SNPs were determined by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） in combination with sequence analysis in 169 patients with post-hepatitis B cirrhosis and 119 healthy controls. The genotypes and allele frequency distribution of these SNPs were then analyzed. RESULTS： TNF-α-308 GG genotype and G allele frequency in patients with post-hepatitis B cirrhosis were signif icantly higher than those in healthy controls （P 〈 0.001, OR 〉 3）. Although there were no significant differences in TGF-β1-509 genotypes between post-hepatitis B patients and healthy controls, the T allele frequency was signif icantly higher in post-hepatitis B patients than in healthy controls （P 〈 0.05）. There were also no signif icant differences in IL-10-592 genotypes and allele frequencies between post-hepatitis B patients and healthy controls. CONCLUSION： The TNF-α-308G/A and TGF- β1-509T/C SNPs may be related to the susceptibility to post-hepatitis B cirrhosis.