INTERGENIC INTERACTIONS OF CYTOKINE GENES IL1, IL1RA, IL6, IL10 AND TNFА IN PATIENTS WITH IRRITABLE BOWEL SYNDROME AND ULCERATIVE COLITIS IN RUSSIAN POPULATION OF THE CHELYABINSK REGION

Сomplex intergenic interactions should be taken into account when predicting the risk of adverse course in a pathological process. This presumption is at the heart of evolving multifactorial diseases (ulcerative colitis and irritable bowel syndrome). A single genetic polymorphism seems to be a weak risk factor when predicting the disease evolution and it could not be used as a prognostic model for development of multifactorial pathologies, especially in cases of rare alleles. However, it is well known that the combination of unfavorable alleles of several genes with an additive effect is dangerous. Therefore, identification of such polymorphisms is very important.
Previously we conducted a test panel, in order to evaluate associations of alleles and genotypes of some cytokine genes (IL1β, TNFα, IL1rа, IL10, IL6) with predisposal, or resistance for ulcerative colitis and irritable bowel syndrome in the Russian Chelyabinsk region. Distribution of alleles and genotypes of these genes have been assessed in irritation bowel disease (IBD) and ulcerative colitis (UC). The following methods were used: isolation of DNA samples from whole blood, genotyping of the studied gene polymorphisms with PCR, RFLP. A comparative analysis of intergenic interactions between the cytokine genes IL1β, TNFα, IL1ra, IL10, IL6 in the IBD and UC patients was carried out by the Multifactor Dimensionality Reduction method. The analysis is based on the use of polymorphic loci of IL1β, TNFα, IL1ra, IL10, IL6 combinations chosen for analysis of intergenic interactions, with respect to the risk for IBS and UC predisposition. As a result of this study, a fourlocus model IL1β(+3953)*Т/TNFα(-308)*A/IL10(-1082)*G/IL6(-174)*G was identified for IBS, which was characterized by 90% repeatability and prediction accuracy of 74.5%. This model of gene interactions between the cytokine IL1β, TNFα, IL1ra, IL10, IL6 genes had the greatest prediction potential (p < 0.001) in IBS, whereas the model for UC was not statistically significant. The following types of genetic interactions were established: synergism between the IL1β(+3953)*Т and TNFα(-308)*A loci, whereas IL6(-174)*G и IL10(-1082)*G, TNFα(-308)*A seem to be in antagonistic relationships. The study made it possible to establish that the -174G/C IL-6 polymorphism may play a central role and provide intergenic interactions with SNPs of IL1β, TNFα, IL10 for predisposal to irritable bowel syndrome in Chelyabinsk Region of Russia.

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