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

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.

Bioinformatics Analysis Using ATAC-seq and RNA-seq for the Identification of 15 Gene Signatures Associated With the Prediction of Prognosis in Hepatocellular Carcinoma

“…SLC1A5 may serve as a potential target for enhancing anti-tumour immunity in the tumour microenvironment ( 27 ). According to the literature, GCLM gene polymorphisms are associated with hepatitis B virus-induced liver disease ( 28 ). There is limited research on BOD1, GDI2, GTF3C6 and ERI3’ impact on hepatocellular carcinomas.…”

Transcriptomic Analysis Reveals Both Coxsackievirus B3 Woodruff and GD Strain Using Similar Key Genes to Induce FoxO Signaling Pathway Activation in HeLa Cells

“…As con rmed in RT-PCR results GADD45B was up regulated during infection and SOD2 is slightly up regulate until 6hpi. The DEG CYBA encoded protein is a crucial subunit of NADPH oxidase involve in oxidative stress, and researchers have studied its role in HCV and HBV disease mechanism 28,29 . In both RNA-seq and RT-PCR result, CYBA was down regulated during virus infection.…”

Liver Cirrhosis in Chronic Hepatitis B Patients Is Associated with Genetic Variations in DNA Repair Pathway Genes

“…Additionally, the T allele was associated with an increase of chromosomal deletions indicative of defects in BER pathway and with a lower survival time of patients with different types of cancer [44][45][46]. Moreover, in vitro and in vivo studies demonstrated that HBV can induce reactive oxygen species (ROS) production that causes oxidative stress resulting in hepatocyte injury [47][48][49]. As XRCC1 is one of the main players in the repair of ROS-induced lesions [50], it brings us to the conclusion that affecting protein function rs25487 may have an impact on HBV-induced liver fibrosis development.…”