THE SIGNIFICANCE OF GENE POLYMORPHISM OF SOME PRO- AND ANTIINFLAMMATORY CYTOKINES IN PATIENTS WITH SEVERE ULCERATIVE COLITIS

Abstract

The objective of the study was too study the polymorphism of TNFa(rs1800629), IL10(1800871, 1800896) ITGA4(rs1143674, rs1449263), ITGB7(rs11574532) genes in patients with severe ulcerative colitis (UC) Materials and methods. The study included 70 people with UC who lived in the Irkutsk region, the Republic of Buryatia and the Zabaikalsky krai. Patients were divided into two groups: patients receiving genetically engineered biological therapy (GIBT; n = 22) and patients receiving basic therapy (n=48). The control consisted of 115 healthy volunteers. The genotypes were studied by real-time PCR. For statistical processing, we used the criterion χ2, the odds ratio (OR), binary logistic regression analysis with the calculation of 95% confidence interval (CI) using the program "IBM SPSS Statistics Version 25.0". Results. Homozygotes of ITGA4(rs1449263)GG had 2.5 times higher chances of developing the disease than carriers of other polymorphic variants (OR = 2,580; 95% CI: 1,129-5,898; χ2 = 5,266; p = 0,022). Patients with extracellular manifestations (ECM) were 3 times more likely to receive GIBT (OR = 3,000; 95% CI: 0,982-9,167; χ2 = 3,878; p = 0,049). IL10 media(1800896)AA prevailed in the group of patients receiving basic therapy (OR = 0,282; 95% CI: 0,089-0,890; χ2 = 5,473; p = 0,020). Subjects with the homozygous variant of ITGA4(rs1143674)CC were 3.5 times more likely to have indications for the administration of GIBT (OR = 3,536; 95% CI: 1,077-11,603; χ2 = 4,576; p = 0,033). The results of binary logistic regression demonstrated that the homozygous genotype of ITGA4(rs1143674)CC and extraintestinal manifestations of the disease were predictors for an unfavorable prognosis of UC accompanied by the GIBT administration. Conclusion. The association of the debut of the disease, smoking, polymorphic variants TNFa(rs1800629), IL10(1800871), ITGB7(rs11574532) with the UC development and clinical manifestations was not revealed. The disease developed 2,5 times faster in homozygote ITGA4(rs1449263)GG than in other genotype carriers. Subjects with polymorphic variant IL10(1800896)AA prevailed in the group of patients with basic therapy. In addition to the previously known extraintestinal manifestations of the disease, the ITGA4 genotype (rs1143674) CC can act as a risk factor for the development of severe UC, requiring the GIBT administration.