TY - JOUR
T1 - Impact of the genes UGT1A1, GSTT1, GSTM1, GSTA1, GSTP1 and NAT2 on acute alcohol-toxic hepatitis
AU - Piekuse, Linda
AU - Lace, Baiba
AU - Kreile, Madara
AU - Sadovska, Lilite
AU - Kempa, Inga
AU - Daneberga, Zanda
AU - Mičule, Ieva
AU - Sondore, Valentina
AU - Keiss, Jazeps
AU - Krumina, Astrida
N1 - Funding Information:
This study was supported by grants from the Latvian Science Council grant Nos. 09.1384 and 10.0010.02. and the European Social Fund project, which supports the doctoral study program and PhD degree qualification in Riga Stradins University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
KW - Alcoholic
KW - Hepatitis
KW - Oxidative stress
KW - Pharmacogenetics
UR - http://www.scopus.com/inward/record.url?scp=84887957121&partnerID=8YFLogxK
U2 - 10.2478/s11535-013-0249-y
DO - 10.2478/s11535-013-0249-y
M3 - Article
AN - SCOPUS:84887957121
SN - 1895-104X
VL - 9
SP - 125
EP - 130
JO - Central European Journal of Biology
JF - Central European Journal of Biology
IS - 2
ER -
