DOI: 10.24075/brsmu.2018.008


Analysis of the association between the RS767455 T>C TNFRSF1A and RS1061622 T>G TNFRSF1B polymorphisms and nonalcoholic steatohepatitis

Topchieva LV1, Kurbatova IV1, Dudaniva OP2, Shipovskaya AA2
About authors

1 Institute of Biology, Karelian Research Center of RAS,
Petrozavodsk, Republic of Karelia

2 Institute of Medicine, Petrozavodsk State University, Petrozavodsk, Republic of Karelia

Correspondence should be addressed: Ludmila Topchieva
ul. Pushkinskaya 11, Petrozavodsk, 198910; ur.liam@76aveihcpot

About paper

Funding: this study was part of the public contract 0221-2017-0049 and was carried out using the equipment of the shared facility Complex Basic and Applied Research of Living Systems in the Arctic of the Institute of Biology, Karelian Research Center. The work was also sponsored by a scholarship of the President of the Russian Federation for young scientists and graduate students engaged in advanced research and development in priority areas of modernization of the Russian economy in 2015-2017 years. The authors also received support from Petrozavodsk State University as part of the efforts for its strategic development in 2013– 2017 (R&D 115070110006, Information reference map 216022450003, registered February 24, 2016) under the project for the Development of Technologies for Diagnostic Screening for Nonalcoholic Fatty Liver Disease in Overweight Patients and Patients with Metabolic Syndrome (ID 9173GU/2015 dated December 15, 2015) of the UMNIK program.

Received: 2017-10-31 Accepted: 2018-03-02

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