Huang Yi-Shin, Chang Chih-Hao, Lin Tai-Ling, Perng Chin-Lin
Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, Taiwan.
Liver Int. 2014 Jul;34(6):931-6. doi: 10.1111/liv.12533. Epub 2014 Apr 4.
BACKGROUND & AIMS: Non-alcoholic fatty liver disease is the most prevalent liver disease in the world. However, the exact mechanisms that lead to development of advanced non-alcoholic steatohepatitis (NASH) are unknown. Oxidative stress may be an important pathogenic factor in NASH. Manganese superoxide dismutase (SOD2) is an important antioxidant phase 2 enzyme that can reduce reactive oxidative substances and protect hepatocytes. In contrast, cytochrome P450 2E1 (CYP2E1) has pro-oxidant activity and may enhance oxidative stress and counteract the effect of SOD2. Little is known regarding the associations of genetic variants of these enzymes with the risk of NASH. We aimed to investigate the association of genetic variants of SOD2 and CYP2E1 with susceptibility to NASH.
Data from 100 patients with NASH, 31 patients with non-alcoholic steatosis (NAS) and 90 healthy controls were analysed. Their DNA was retrieved for genotyping SOD2 47T>C and CYP2E1 -1053C>T variation by polymerase chain reaction.
There was no statistical difference in the frequency distributions of SOD2 and CYP2E1 genotypes among the NASH, NAS and control groups. However, the frequency of the SOD2 C variant was significantly higher in the NASH group than in the NAS and control groups (22% vs. 14.5% and 11.1%, respectively; P = 0.015). After adjustment for confounders, the SOD2 C/C and C/T genotypes remained associated with the risk of NASH (odds ratio, 2.81; 95% confidence interval, 1.37-5.76; P = 0.005).
The anti-oxidative SOD2 47T>C genetic variant might increase susceptibility to NASH in Chinese. Individuals with the SOD2 C variant may have a higher risk for NASH.
非酒精性脂肪性肝病是全球最常见的肝脏疾病。然而，导致晚期非酒精性脂肪性肝炎（NASH）发生的确切机制尚不清楚。氧化应激可能是NASH的一个重要致病因素。锰超氧化物歧化酶（SOD2）是一种重要的抗氧化第二阶段酶，可减少活性氧化物质并保护肝细胞。相比之下，细胞色素P450 2E1（CYP2E1）具有促氧化活性，可能会增强氧化应激并抵消SOD2的作用。关于这些酶的基因变异与NASH风险之间的关联知之甚少。我们旨在研究SOD2和CYP2E1的基因变异与NASH易感性之间的关联。
分析了100例NASH患者、31例非酒精性脂肪变性（NAS）患者和90例健康对照的数据。通过聚合酶链反应提取他们的DNA，对SOD2 47T>C和CYP2E1 -1053C>T变异进行基因分型。
NASH组、NAS组和对照组中SOD2和CYP2E1基因型的频率分布无统计学差异。然而，NASH组中SOD2 C变异的频率显著高于NAS组和对照组（分别为22%、14.5%和11.1%；P = 0.015）。在对混杂因素进行调整后，SOD2 C/C和C/T基因型仍与NASH风险相关（比值比，2.81；95%置信区间，1.37 - 5.76；P = 0.005）。
抗氧化的SOD2 47T>C基因变异可能会增加中国人患NASH的易感性。携带SOD2 C变异的个体患NASH的风险可能更高。
