BACKGROUND: Only a minority of alcoholics develop alcoholic liver disease (ALD) and allelic variants within genes encoding glutathione-S-transferases (GST) have been associated with ALD vulnerability with controversial results. AIM: To assess the effects of GST polymorphisms on ALD by means of a genetic association study and meta-analysis. METHODS: We retrieved published studies on the relationship between allelic variants within GST genes and ALD by means of electronic database search. A meta-analysis was conducted in a fixed or random effects model. Calculations of odds ratios (OR) and their confidence intervals (CI), tests for heterogeneity of the results and sensitivity analysis, have been performed. A genetic association study comparing GSTM1, GSTT1 and GSTP1 genotype distribution among 279 alcoholics with or without ALD and 144 controls was also performed. Results Fifteen previous studies were identified analysing the association of ALD with polymorphisms within GST genes. After meta-analysis, we found a significant association between the possession of the GSTM1 null allele and the presence of ALD (OR=1.43; 95% CI: 1.14, 1.78; P=0.002) among alcoholic patients. A significant association was also found for the possession of the GSTP1 Val/Val genotype and the presence of ALD (OR=2.04; 95% CI: 1.09, 3.80; P=0.03). CONCLUSIONS: Our results suggest that, among alcoholics, carriers of GSTM1 null genetic variant or Val/Val genotype of Ile/Val GSTP1 polymorphism have an increased risk to suffer from alcoholic liver disease. The role of glutathione-S-transferase as a potential therapeutic target in alcoholic liver disease is reinforced.
BACKGROUND: Only a minority of alcoholics develop alcoholic liver disease (ALD) and allelic variants within genes encoding glutathione-S-transferases (GST) have been associated with ALD vulnerability with controversial results. AIM: To assess the effects of GST polymorphisms on ALD by means of a genetic association study and meta-analysis. METHODS: We retrieved published studies on the relationship between allelic variants within GST genes and ALD by means of electronic database search. A meta-analysis was conducted in a fixed or random effects model. Calculations of odds ratios (OR) and their confidence intervals (CI), tests for heterogeneity of the results and sensitivity analysis, have been performed. A genetic association study comparing GSTM1, GSTT1 and GSTP1 genotype distribution among 279 alcoholics with or without ALD and 144 controls was also performed. Results Fifteen previous studies were identified analysing the association of ALD with polymorphisms within GST genes. After meta-analysis, we found a significant association between the possession of the GSTM1 null allele and the presence of ALD (OR=1.43; 95% CI: 1.14, 1.78; P=0.002) among alcoholicpatients. A significant association was also found for the possession of the GSTP1 Val/Val genotype and the presence of ALD (OR=2.04; 95% CI: 1.09, 3.80; P=0.03). CONCLUSIONS: Our results suggest that, among alcoholics, carriers of GSTM1 null genetic variant or Val/Val genotype of Ile/Val GSTP1 polymorphism have an increased risk to suffer from alcoholic liver disease. The role of glutathione-S-transferase as a potential therapeutic target in alcoholic liver disease is reinforced.
Authors: Whitney S Theis; Kelly K Andringa; Telisha Millender-Swain; Dale A Dickinson; Edward M Postlethwait; Shannon M Bailey Journal: Redox Biol Date: 2013-11-28 Impact factor: 11.799