Metabolic and Steatohepatitis
Genetic variations of superoxide dismutase 2 and cytochrome P450 2E1 in non-alcoholic steatohepatitis
Article first published online: 4 APR 2014
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 34, Issue 6, pages 931–936, July 2014
How to Cite
Liver Int. 2014: 34: 931–936
- Issue published online: 17 JUN 2014
- Article first published online: 4 APR 2014
- Accepted manuscript online: 20 MAR 2014 01:40PM EST
- Manuscript Accepted: 13 MAR 2014
- Manuscript Received: 9 DEC 2013
- Taipei Veterans General Hospital. Grant Numbers: V101C-055, V102C-056
- cytochrome P450 2E1;
- fatty liver;
- genetic variation;
- non-alcoholic fatty liver disease;
- non-alcoholic steatohepatitis;
- non-alcoholic steatosis;
- superoxide dismutase 2
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.