-174g>c polymorphism (rs1800795) of il6 gene and its impact on the effectiveness of treatment with ursodeoxycholic acid in patients with nonalcoholic steatohepatitis
Abstract
The aim was a comparative analysis of clinical and laboratory parameters in carriers of different genotypes for the -174G>C IL6 gene polymorphic marker (rs1800795) in healthy donors and patients with NASH in the absence of hepatoprotective therapy and after therapy with UDCA. There were examined 50 patients with the diagnosis of NASH. NASH patients were treated with UDCA at a dose of 10-15 mg/kg for 8-10 weeks. The control group consisted of 50 donors without the clinical manifestations of NAFLD. Genotyping was carried out using the PCR-RFLP method. Functional liver tests, the level of cytokines IL6 and TNFα in the blood, the level of expression of the IL6 and TNF genes, the activity of caspases in peripheral leukocytes were estimated before the treatment and after UDCA monotherapy. In NASH patients with different alleles for the -174G>C IL6 gene polymorphic marker, there are significant differences in the level of the indicator of hepatic cell damage - AST, and the mRNA level of the TNF gene in PBL. In carriers of C allele, the effect of UDCA therapy on the level of AST and the TNF gene transcripts in PBL is less pronounced than in carriers of the GG genotype. This indicates a lower sensitivity to UDCA therapy in carriers of the mutant allele. The medians of decrease in the AST level and in the level of mRNA relative expression of the TNF gene in carriers of C allele are significantly lower than in carriers of the GG genotype, p<0.05. Significant differences in the effect of UDCA therapy on the level of other studied parameters depending on the genotype were not found. The presence of the -174G>C single nucleotide substitution in the IL6 gene (rs1800795), which is associated with the development of NASH, can determine not only the genetic predisposition to the development of this disease, but also the different sensitivity of patients with NAFLD to UDCA-based drugs.
About the Authors
I. V. Kurbatova
Institute of Biology of Karelian Research Centre Russian Academy of Sciences
Russian Federation
Russian Federation
O. P. Dudanova
Petrozavodsk State University, the Department of Internal Medicine Propaedeutics and hygiene
Russian Federation
Russian Federation
L. V. Topchieva
Institute of Biology of Karelian Research Centre Russian Academy of Sciences
Russian Federation
Russian Federation
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Review
For citations:
Kurbatova I.V., Dudanova O.P., Topchieva L.V. -174g>c polymorphism (rs1800795) of il6 gene and its impact on the effectiveness of treatment with ursodeoxycholic acid in patients with nonalcoholic steatohepatitis. Experimental and Clinical Gastroenterology. 2018;(2):31-36. (In Russ.)
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