Methylation of the Glutathione-S-Transferase P1 Gene Promoter Is Associated with Oxidative Stress in Patients with Chronic Hepatitis B

Abstract

Glutathione-S-transferase P1 (GSTP1) and glutathione-S-transferase M3 (GSTM3) catalyze the glutathione-related clearance of xenobiotics. The methylation of these gene promoters was associated with oxidative stress that induced liver damage. This study aims to explore the relationship among GSTP1 and GSTM3 methylation, DNA methyltransferases (DNMTs) expression, and oxidative stress in patients with chronic hepatitis B (CHB). We retrospectively enrolled 153 patients with CHB and 40 healthy controls (HCs). The GSTP1 and GSTM3 methylation status, DNMTs mRNA levels in peripheral mononuclear cells (PBMCs) and TNF-α and malondialdehyde (MDA) levels in plasma were detected. GSTP1 methylation was significantly higher in patients with CHB than HCs (P = 0.047). Patients with HBeAg-positive CHB showed significantly higher GSTP1 methylation than those with HBeAg-negative CHB (P = 0.017) and HCs (P = 0.007). No significant difference was observed between GSTP1 methylation in HBeAg-negative CHB and HCs (P = 0.191). DNMT1 and DNMT3a mRNA levels were significantly higher in participants with GSTP1 methylation than those without. In patients with CHB, the degree of GSTP1 promoter methylation was significantly correlated with DNMT1 mRNA, DNMT3a mRNA, TNF-α, MDA, HBeAg, ALT, AST and TBIL. In contrast, no significant difference was found between GSTM3 methylation in patients with CHB and HCs (P = 0.079). Meanwhile, no significant difference could be observed between GSTM3 promoter methylation in patients with HBeAg-positive CHB and HBeAg-negative CHB (P = 0.146). Therefore, this study demonstrated that GSTP1 hypermethylation was associated with DNMT1, DNMT3a overexpression and oxidative stress in patients with HBeAg-positive CHB.

Hepatitis E Virus Induces Hepatocyte Apoptosis via Mitochondrial Pathway in Mongolian Gerbils

“…A dysfunction of the mitochondrial antioxidant system may render mitochondria susceptible to injuries despite the adequate cytosolic antioxidant levels ( Cano et al, 2014 ). Viral infections were shown to induce mitochondrial damage and oxidative stress ( Acar et al, 2009 ; Khadem Ansari et al, 2015 ; Fan et al, 2016 ), which was confirmed in this study as well, since the SOD activity was shown to decreased while MDA concentrations increased in HEV-infected groups. Our combined results support the conclusion that HEV infection induces mitochondrial damage, which leads to oxidative stress development.…”

Prenatal fine particulate exposure associated with reduced childhood lung function and nasal epithelia GSTP1 hypermethylation: Sex-specific effects

“…Air pollution exposure generates reactive oxygen species (ROS) and the resulting oxidant imbalance is thought to be a central pathway mediating the association between air pollution exposure and impaired lung function [ 42 , 43 ]. GSTP1 controls enzymes involved in the detoxification of ROS [ 44 ] - GSTP1 variants are more susceptible to the health effects of air pollution, including lung function, [ 45 ] and GSTP1 methylation is associated with oxidative stress [ 46 ]. The developing fetus is especially prone to oxidative injury, as antioxidant defenses remain immature through pregnancy; male fetuses may be at even increased risk.…”

Identification of chicken FSHR gene promoter and the correlations between polymorphisms and egg production in Chinese native hens

“…Studies have shown that FSHR is selectively expressed in Sertoli cells and ovarian granulosa cells (Camp, Rahal, & Mayo, ; Dankbar et al, ), and its expression level is closely related to germ cell differentiation and maturation (Heckert & Griswold, ). Gene promoters play a significant role in transcriptional regulation (Fan et al, ; Wang et al, ). At present, the FSHR promoter of humans, rats, mice and sheep has been successfully cloned (Gromoll, Dankbar, & Gudermann, ; Heckert, Daley, & Griswold, ; Levallet, Koskimies, Rahman, & Huhtaniemi, ; Sairam & Subbarayan, ), and the mechanism of transcriptional regulation has been extensively studied.…”