Dorofieieva H. Identification of diagnostic molecular biological markers of the genome and the intestinal microbiome development of ulcerative colitis in elderly patients

In this dissertation solved relevant issues of study and development of molecular biological markers of the genome and microbiome associated with development of ulcerative colitis in the elderly to Refine and enhance existing data of the occurrence and characteristics of the flow of ulcerative colitis, which can be considered as one of the conditions of the definition and compilation of clinical Protocol of treatment of this disease. Was evaluated the frequency of polymorphic variants of genes – NOD2/CARD, TOLL-like receptors (TLR2/TLR3/TLR4), IL10, JAK2 in patients with ulcerative colitis in different age groups, the changes in the mucous barrier of the intestine, the qualitative and quantitative composition of mucus in ulcerative colitis in different age groups, the features of the microbiome in patients with ulcerative colitis in different age categories with the study SIBR, microbial interation and regulatory bacteria, the influence of genetic polymorphism on the intestinal microbiome in patients with ulcerative colitis with early and late disease the proposed molecular genetic markers for ulcerative colitis in different age groups. Determined the prevalence of homozygous variations of the TLR2 gene in patients with early debut of the ulcerative colitis and heterozygote variant of the TLR2 polymorphism in patients with late onset of the disease, the heterozygous variants of the gene TLR4 and the prevalence of polymorphic variants Asp299Gly in patients with early debut of ulcerative colitis, indicators homozygous genotype at both polymorphic variants of the gene TLR4 in the prevalence of the polymorphic variant Thr399Ile in patients with late debut ulcerative colitis. When individual SNP analysis identified that patients with early debut of ulcerative colitis prevalent homozygous polymorphic variant AA Arg753Gln TLR2 gene, and patients with late-onset disease were more likely to be heterozygous AG variant polymorphism of TLR2. Patients with early onset ulcerative colitis dominated homozygous polymorphic variants (PP and LL) Phe412Leu TLR3 in patients with late debut ulcerative colitis heterozygous variant (PL) TLR3, respectively. The analysis of the intestinal microbiome in ulcerative colitis in different age categories (bacterial overgrowth syndrome and microbial enterotomy) found that the degree of activity of ulcerative colitis has a significant impact on the composition of the intestinal microbiome. Using the determination of the main correlation relationships, we evaluated the effect of the genetic predisposition and changes in the microbiome on the morphological and functional features of the large intestine mucosa in ulcerative colitis of different age groups.