BIOMEDICAL JOURNAL OF PIROGOV RNRMU (MOSCOW, RUSSIA)
Analysis of the association between the RS767455 T>C TNFRSF1A and RS1061622 T>G TNFRSF1B polymorphisms and nonalcoholic steatohepatitis
Poor diet, sedentary behavior and genetic background are major factors contributing to the etiology and pathogenesis of non-alcoholic fatty liver disease (NAFLD). It is hypothesized that polymorphisms of the TNFRI and TNFRII genes coding for the receptors that bind the proinflammatory cytokine tumor necrosis factor alpha (TNFα) can be implicated in the susceptibility to NAFLD, but not much data is available in the literature. In the present work we aimed to investigate a possible association between the rs767455 T>C TNFRSF1A and rs1061622 T>G TNFRSF1B polymorphisms and one of NAFLD forms, nonalcoholic steatohepatitis (NASH), and to assess their effect on blood biochemistry. Samples of DNA isolated from the venous blood of 151 healthy donors and 242 patients with NASH were genotyped using PCR-RFLP. TNFα concentrations were measured by ELISA. We have not found any association between the rs767455 T>C TNFRSF1A polymorphism and the development of NASH in the residents of Karelia. However, we have discovered an association between NASH and the T>G TNFRSF1B rs1061622 polymorphism. Carriers of the G allele have a higher risk of developing NASH (OR = 4.83; 95% CI: 2.72–8.57). The rs1061622 T>G genotype of the TNFRSF1B gene appears to have no effect on TNFα concentrations and the activity of alanineaminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP). Our findings suggest a possible association between the rs1061622 T>G TNFRSF1B polymorphism and a risk of developing NASH in the residents of Karelia.
Keywords: non-alcoholic steatohepatitis, tumor necrosis factor alpha, tumor necrosis factor alpha receptors, mbTNFRI, sTNFR, TNFRSF1A gene, TNFRSF1B gene, gene polymorphism, alanine aminotransferase, aspartate aminotransferase