Front Genet. 2020 Jan 8;10:1290. doi: 10.3389/fgene.2019.01290. eCollection 2019.
Oxidative Stress-Related Gene Polymorphisms Are Associated With Hepatitis B Virus-Induced Liver Disease in the Northern Chinese Han Population.
Ma N1, Liu W1, Zhang X1, Gao X1, Yu F2, Guo W1, Meng Y3, Gao P4, Zhou J4, Yuan M4, Mi Y4, Zhang L4, Qi S4, Li L4, Wang L1, Su Q5, Yang L1, Liu D1.
Author information
1
Hebei Key Laboratory of Environment and Human Health, Department of Epidemiology and Statistics, School of Public Health, Hebei Medical University, Shijiazhuang, China.
2
The Hebei Key Laboratory of Gastroenterology, Division of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
3
Antenatal Diagnosis Center, The Fourth Hospital of Shijiazhuang, Shijiazhuang, China.
4
Hebei Key Laboratory of Environment and Human Health, Department of Social Medicine and Health Care Management, School of Public Health, Hebei Medical University, Shijiazhuang, China.
5
School of Basic Medicine, Hebei Medical University, Shijiazhuang, China.
Abstract
Oxidative stress is closely related to the occurrence and development of various diseases such as cancer, diabetes, and cardiovascular and infectious diseases. We identified six critical genetic variants related to oxidative stress, and evaluated their main effects and their interaction effects on hepatitis B virus (HBV)-induced liver diseases. We enrolled 3,128 Han Chinese subjects into five groups: healthy controls, chronic hepatitis B (CHB), liver cirrhosis (LC), hepatocellular carcinoma (HCC), and natural clearance. We then determined the genotypes in each group for CYBA-rs4673, NCF4-rs1883112, NOX4-rs1836882, rs3017887, SOD2-rs4880, and GCLM-rs41303970, and evaluated the association between these variants and HBV-induced liver diseases. Gene-gene interactions were evaluated using generalized multifactor dimensionality reduction, logistic regression, and four-by-two tables. Significant associations were observed between healthy controls and the CIB group (CHB+LC+HCC). The CYBA-rs4673AG genotype was associated with a 1.356 rate of susceptibility of HBV-induced liver disease compared to the wild type GG genotype. The NCF4-rs1883112G allele occurred more frequently in healthy controls than in the CIB group in all three models (dominant, codominant, and recessive). Nox4-rs1836882 TC showed a protective association, being more frequent in healthy controls compared to the wild type TT genotype. GCLM-rs41303970A was associated with HBV-induced liver disease. The overall best model by multifactor dimensionality reduction was a five factor interaction model that had the highest cross validation consistency (10/10) and test accuracy (0.5669), P = 0.001. Oxidative stress-related gene polymorphisms are likely to be associated with HBV-induced liver disease, suggesting that information on these variations is useful for risk assessment of HBV-induced liver disease.