Kyrian O. A.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Ulcerative colitis is an inflammatory bowel disease with complex pathogenetic mechanisms. It increases the risk of colon cancer in a case of the long-term inflammation. Sporadic forms of cancer develop more frequently because of the adenoma-carcinoma sequence if there is no inflammation, however, matrix metalloproteinases play an important role in both inflammation initiation and in neoplasia. The purpose of this article is to describe the research of peculiarities of the MMP-1, MMP-3, MMP-9 and TIMP1 influence on the development and the course of the ulcerative colitis and adenomatous polyps of the colon in patients of the Poltava region. During the research, the hereditary predisposition to the disease and its dependency on the TIMP-1 С536Т (rs11551797), MMP-9 -8202A/G (rs11697325) single nucleotide polymorphism (SNP) was analyzed. 89 patients were involved in the research: 53 (59.6%) with ulcerative colitis, 36 (40.4%) with adenomatous polyps and 49 healthy people. MMP-1, MMP-3, MMP-9, and blood serum TIMP-1 were quantified with the ELISA assay. MMP-9 A-8202G (rs11697325) and TIMP-1 С536Т (rs11551797) SNP were analyzed with the PCR method using the DNA sample of the whole venous blood. The correlation was established between the patients with adenomatous polyps and with the G/G genotype of ММР-9 -8202A/G (rs1169732)(χ2=9,82, р<0,007) SNP. A significant increase of MMP-1 level in blood (p<0,05) was also detected, as well as MMP-1/TIMP-1 ratio in comparison with the control group. The increased level of MMP-9 (р<0,01)(r=0,79) and ММР-1 (р<0,02) was found in patients with the ulcerative colitis. This appeared to be most marked in patients with highly active disease. The difference between the MMP-1/TIMP-1 ratio of the groups remained as well, and also the MMP-9/TIMP-1 ration increased especially in a case of highly active disease (р<0,01)(r=0,82). The increased expression of MMP-1 in blood serum therefore can be regarded as one of the markers associated with the development of colon adenoma, and the G/G genotype of MMP-9 (-8202А/G) can be considered as the marker of the adenoma development in healthy people and as the neoplasia biomarker in patients with ulcerative colitis. The increase expression of MMP-9 and the imbalance in the ratio of MMP-9/TIMP-1 in blood serum in patients with ulcerative colitis is considered an unfavorable prognostic marker.

matrix metalloproteinases,adenomatous polyps,inflammation,ulcerative colitis

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«Bulletin of problems biology and medicine» Issue 4 (167), 2022 year, 167-178 pages, index UDK 616.348-002-006.6

10.29254/2077-4214-2022-4-167-167-178