AUTHOR=Ma Ning , Liu Wenxuan , Zhang Xiaolin , Gao Xia , Yu Fengxue , Guo Weiheng , Meng Yanxin , Gao Ping , Zhou Jin , Yuan Meina , Mi Yingjun , Zhang Lei , Qi Sufen , Li Lu , Wang Luyao , Su Qiao , Yang Lei , Liu Dianwu 

TITLE=Oxidative Stress-Related Gene Polymorphisms Are Associated With Hepatitis B Virus-Induced Liver Disease in the Northern Chinese Han Population

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01290

DOI=10.3389/fgene.2019.01290

ISSN=1664-8021

ABSTRACT=<p>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 <italic>CYBA</italic>-<italic>rs4673</italic>, <italic>NCF4</italic>-<italic>rs1883112</italic>, <italic>NOX4</italic>-<italic>rs1836882</italic>, <italic>rs3017887</italic>, <italic>SOD2</italic>-rs<italic>4880</italic>, and <italic>GCLM</italic>-<italic>rs41303970</italic>, 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 <italic>CYBA</italic>-<italic>rs4673</italic>AG genotype was associated with a 1.356 rate of susceptibility of HBV-induced liver disease compared to the wild type GG genotype. The <italic>NCF4</italic>-<italic>rs1883112</italic>G allele occurred more frequently in healthy controls than in the CIB group in all three models (dominant, codominant, and recessive). <italic>Nox4</italic>-<italic>rs1836882</italic> TC showed a protective association, being more frequent in healthy controls compared to the wild type TT genotype. <italic>GCLM</italic>-<italic>rs41303970</italic>A 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), <italic>P</italic><italic>=</italic> 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.</p>