Pastor Isabel J, Laso F Javier, Romero Alfonso, González-Sarmiento Rogelio
Unidad de Medicina Molecular-Departamento de Medicina, Instituto de Neurociencias de Castile and León,Universidad de Salamanca, Spain.
Alcohol Clin Exp Res. 2005 Nov;29(11):1928-31. doi: 10.1097/01.alc.0000187595.19324.ca.
The tumor necrosis factor alpha gene (TNFA) has been recently associated to alcoholic steatohepatitis. We have analyzed the distribution of genotypes and alleles of two polymorphisms at positions -238 and -308 in the promoter region of the TNFA gene in a Spanish male population of alcoholics with and without alcoholic liver cirrhosis.
149 male alcoholics (84 without alcoholic liver disease, and 65 with alcoholic liver cirrhosis) and 90 control subjects were included. Genotyping was done by polymerase chain reaction and digestion with restriction enzymes.
No significant differences in the distribution of genotypes and alleles of the -308 TNFA gene polymorphism were observed between alcoholics and non-alcoholics, or between alcoholics with liver cirrhosis and those without liver disease. However, we found an association between the -238 TNFA polymorphism and alcoholic liver cirrhosis; the frequency of the heterozygous genotype being significantly higher in alcoholics with cirrhosis than in those without liver damage.
The -238 TNFA-A allele is associated with a higher risk to develop alcoholic liver cirrhosis. This polymorphism could be considered as a genetic factors that confer predisposition to suffer liver cirrhosis in the alcoholic population of Castile and León.
肿瘤坏死因子α基因(TNFA)最近被认为与酒精性脂肪性肝炎有关。我们分析了西班牙男性酗酒人群中TNFA基因启动子区域-238和-308位点两个多态性的基因型和等位基因分布情况,这些酗酒者有的患有酒精性肝硬化,有的未患。
纳入149名男性酗酒者(84名无酒精性肝病,65名有酒精性肝硬化)和90名对照者。通过聚合酶链反应和限制性酶切进行基因分型。
在酗酒者与非酗酒者之间,以及有肝硬化的酗酒者与无肝病的酗酒者之间,未观察到-308 TNFA基因多态性的基因型和等位基因分布有显著差异。然而,我们发现-238 TNFA多态性与酒精性肝硬化之间存在关联;肝硬化酗酒者中杂合基因型的频率显著高于无肝损伤的酗酒者。
-238 TNFA -A等位基因与发生酒精性肝硬化的较高风险相关。这种多态性可被视为在卡斯蒂利亚-莱昂的酗酒人群中易患肝硬化的一个遗传因素。