Sazci Ali, Ozel Mavi Deniz, Ergul Emel, Aygun Cem
1 Department of Medical Biology and Genetics, Faculty of Medicine, University of Kocaeli , Kocaeli, Turkey .
Genet Test Mol Biomarkers. 2013 Nov;17(11):849-53. doi: 10.1089/gtmb.2013.0309. Epub 2013 Aug 21.
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of a history of alcohol use and with a prevalence of 15%-45% in developed nations. Nonalcoholic steatohepatitis (NASH) is an advanced stage of NAFLD with a pronounced major inflammatory component. The aim of this study was to investigate the possible role of nicotinamide-N-methyltransferase (NNMT) gene rs694539 variant in the development of NASH. Therefore, we analyzed 80 NASH patients and 183 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism method developed in our laboratory. The NNMT rs694539 variant was found to be significantly associated with NASH (χ(2)=9.349, p=0.009). The individuals with the GG genotype had protection against NASH (χ(2)=3.793, p=0.051, odds ratio [OR]=0.580, 95% confidence interval [CI]=0.334-1.006), whereas the individuals with the AA genotype showed statistically significant increased risk for NASH (χ(2)=7.748, p=0.005, OR=7.338, 95% CI=1.448-37.190). Moreover, the G allele was protective against NASH (χ(2)=7.748, p=0.005, OR=0.136, and 95% CI=0.027-0.691). On the other hand, the A allele was a risk factor for NASH (χ(2)=3.793, p=0.051, OR=1.725, and 95% CI=0.994-2.996). Consequently, the rs694539 variant of NNMT gene is a genetic risk factor for developing NASH.
非酒精性脂肪性肝病（NAFLD）是无饮酒史情况下肝脏脂肪变性异常最常见的病因，在发达国家患病率为15% - 45%。非酒精性脂肪性肝炎（NASH）是NAFLD的晚期阶段，具有明显的主要炎症成分。本研究的目的是调查烟酰胺 - N - 甲基转移酶（NNMT）基因rs694539变异体在NASH发生发展中的可能作用。因此，我们使用在我们实验室开发的聚合酶链反应 - 限制性片段长度多态性方法分析了80例NASH患者和183例健康对照。发现NNMT rs694539变异体与NASH显著相关（χ(2)=9.349，p = 0.009）。携带GG基因型的个体对NASH有保护作用（χ(2)=3.793，p = 0.051，比值比[OR]=0.580，95%置信区间[CI]=0.334 - 1.006），而携带AA基因型的个体患NASH的风险在统计学上显著增加（χ(2)=7.748，p = 0.005，OR = 7.338，95% CI = 1.448 - 37.190）。此外，G等位基因对NASH有保护作用（χ(2)=7.748，p = 0.005，OR = 0.136，95% CI = 0.027 - 0.691）。另一方面，A等位基因是NASH的危险因素（χ(2)=3.793，p = 0.051，OR = 1.725，95% CI = 0.994 - 2.996）。因此，NNMT基因的rs694539变异体是发生NASH的遗传危险因素。
