Cirrhosis pathogenesis: Polymorphism of glutathione S-transferase genes

We tested the association of deletion polymorphism in the GSTT1 and GSTM1 genes for glutathione S-transferases and the A313G single-nucleotide polymorphism in the GSTP1 gene with cirrhosis morbidity and 4-year survival rate among residents of the Tomsk region, West Siberia. The homozygous deletion of the GSTM1 gene (null genotype) proved to be a protective factor against alcoholic and mixed (viral and alcoholic) liver cirrhosis. The frequency of this genotype in patients of the combined group having cirrhosis of any etiology was 39.2%, in patients with alcoholic cirrhosis it was 39.0%, and in patients with mixed cirrhosis it was 34.2%. This genotype was much more frequent among patients of the control group: 64.6%. The GSTM1 null genotype and the GSTP1 A313G polymorphic variant correlated with survival rate. The survivors had a higher GSTM1 null genotype frequency than the dead patients, 46.6 and 30.2%, respectively; a higher frequency of the GSTP1 AA genotype, 63.1 and 40.5%; and a lower frequency of the GSTP1 AG (A313G) genotype (31.1 and 51.2%). The survival rate in patients with the GSTP1 AA genotype was 2.5 times as high as in GG or AG genotype carriers. In patients with the GSTM1 null genotype, the survival rate was twice as high as in patients without the deletion. The 4-year fatal case probability in patients having the heterozygous GSTP1 AG genotype was 2.3 times higher than in patients with the homozygous AA or GG genotypes.