Genetic variations of superoxide dismutase 2 and cytochrome P450 2E1 in non-alcoholic steatohepatitis

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 sup...

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Bibliographic Details
Published in:Liver international 2014-07, Vol.34 (6), p.931-936
Main Authors: Huang, Yi-Shin, Chang, Chih-Hao, Lin, Tai-Ling, Perng, Chin-Lin
Format: Article
Language:English
Subjects:
Adult
Asian Continental Ancestry Group - genetics
Case-Control Studies
China - epidemiology
Cytochrome P-450 CYP2E1 - genetics
cytochrome P450 2E1
fatty liver
Female
Genetic Predisposition to Disease
Genetic Variation
Humans
Male
Middle Aged
non-alcoholic fatty liver disease
Non-alcoholic Fatty Liver Disease - enzymology
Non-alcoholic Fatty Liver Disease - ethnology
Non-alcoholic Fatty Liver Disease - genetics
non-alcoholic steatohepatitis
non-alcoholic steatosis
Phenotype
Risk Factors
Superoxide Dismutase - genetics
superoxide dismutase 2
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Summary: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. Methods 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. Results 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). Conclusions 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.
ISSN:1478-3223
1478-3231
DOI:10.1111/liv.12533