Impact of the genes UGT1A1, GSTT1, GSTM1, GSTA1, GSTP1 and NAT2 on acute alcohol-toxic hepatitis

Abstract

Alcohol metabolism causes cellular damage by changing the redox status of cells. In this study, we investigated the relationship between genetic markers in genes coding for enzymes involved in cellular redox stabilization and their potential role in the clinical outcome of acute alcohol-induced hepatitis. Study subjects comprised 60 patients with acute alcohol-induced hepatitis. The control group consisted of 122 healthy non-related individuals. Eight genetic markers of the genes UGT1A1, GSTA1, GSTP1, NAT2, GSTT1 and GSTM1 were genotyped. GSTT1 null genotype was identified as a risk allele for alcohol-toxic hepatitis progression (OR 2.146, P=0.013). It was also found to correlate negatively with the level of prothrombin (β= −11.05, P=0.037) and positively with hyaluronic acid (β=170.4, P=0.014). NAT2 gene alleles rs1799929 and rs1799930 showed opposing associations with the activity of the biochemical markers γ-glutamyltransferase and alkaline phosphatase; rs1799929 was negatively correlated with γ-glutamyltransferase (β=−261.3, P=0.018) and alkaline phosphatase (β= −270.5, P=0.032), whereas rs1799930 was positively correlated with Γ-glutamyltransferase (β=325.8, P=0.011) and alkaline phosphatase (β=374.8, P=0.011). Enzymes of the glutathione S-transferase family and NAT2 enzyme play an important role in the detoxification process in the liver and demonstrate an impact on the clinical outcome of acute alcohol-induced hepatitis.

Differences in proteomic profiles between yak and three cattle strains provide insights into molecular mechanisms underlying high‐altitude adaptation

“…Higher expression levels of NDUFV1 and Cx III would support a robust heart function in yak. ALDH directly participates in alcohol metabolism (Edenberg, 2007), and GST contributes to the maintenance of redox status after alcohol exposure (Piekuse et al, 2014). Enhanced expression of these two proteins would minimize the harmful effects of alcohol accumulation in yak under low oxygen conditions.…”