SIRT1基因多态性与BMI及酒精性肝病相关性的研究

Correlation of SIRT1 Gene Polymorphism with BMI for the Risk of Alcoholic Fatty Liver Disease

为探讨SIRT1基因多态性与BMI及酒精性脂肪肝病的相关性,选取268例重度饮酒者,依据是否患有酒精性脂肪肝,分为酒精性脂肪肝病组(n=176)和饮酒对照组(n=92);237例轻度饮酒或不饮酒者,分为非酒精性脂肪肝病组(n=117)和健康对照组(n=120),收集患者的基本信息及相关临床资料;选择SIRT1四组核苷酸片段,命名为rs33957861、rs11599176、rs12413112、rs35689145,用西格诺质谱分析平台检测SIRT1基因类型。结果显示,与饮酒对照组和健康对照组比,rs33957861、rs11599176、rs12413112明显降低非酒精性脂肪肝病(NAFLD)和酒精性脂肪肝病(AFLD)的发病风险,而rs35689145增加其发病风险;单倍型AAAA、AAGA、CAGA、CGAA可降低AFLD的发生风险,而CAAG增加AFLD的发病风险。另外,在NAFLD和AFLD组中,rs33957861、rs11599176、rs12413112突变基因型携带者较野生型体重指数(BMI)低,而rs35689145中,突变基因型携带者较野生型BMI高(P<0.05)。而且,rs33957861 C>T,rs11599176 A>G和体重指数是AFLD的独立风险因子。由此可知,SIRT1基因多态性与酒精性脂肪肝发病相关,在酒精性脂肪肝病患者中,四组核苷酸和体重指数密切相关。

To investigate the correlation between SIRT1 single nucleotide polymorphisms(SNPs)with BMI and the risk of alcoholic fatty liver disease(AFLD),a total of 268 heavy drinkers were divided into AFLD group(n=176)and Alcoholic control group(n=92),and 237 light-or non-drinkers into NAFLD group(n=117)and Health control group(n=120),and the basic information of the subjects were collected and clinical examinations were measured.The genotype of SIRT1 was detected through Sequenom MassARRAY iPLEX test.The results showed that compared with the Alcoholic and Health controls,three SNPs of SIRT1 gene(i.e.,rs33957861,rs11599176 and rs12413112)significantly reduced the risk of NAFLD and AFLD and one SNPs(i.e.,rs35689145)remarkably increased the risk;the haplotypes of AAAA,AAGA,CAGA,CGAA were lower in the occurrence of AFLD,while the haplotype of CAAG was higher in the occurrence of AFLD.The analysis also found that the mutant genotype carriers in rs33957861,rs11599176 and rs12413112 in NAFLD and AFLD groups decreased in BMI,but in that of the rs35689145 increased in BMI when compared to those with the wild-type homozygous genotype carriers.Specially,it was indicated that the C>T of rs33957861 and A>G of rs11599176 were two independent risk factors of AFLD.Conclusively,SNPs of SIRT1 was correlated with the risk of AFLD and there was a close correlation between four SNPs and BMI in AFLD patients.