Genetic and morphological aspects of the enterocutaneous fistula development

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Objective. To analyze the frequency of polymorphic variants of matrix metalloproteinase-2 (C-1306 → T) and tissue inhibitors of metalloproteinase-2 (G303 → A) genes in patients with enterocutaneous fistulas and to identify the connection with morphological changes of connective tissue.
 Materials and methods. The object of the study comprises 24 patients with enterocutaneous fistula who were treated in the Shalimov National Institute of Surgery and Transplantology during 2016-2020. Laboratory, genetic, histological studies and statistical analysis were performed.
 Results. As a result of genetic and statistical analysis of the matrix metalloproteinase-2 (C-1306→T) and tissue inhibitors of metalloproteinase-2 (G303→A) gene single nucleotide polymorphisms, genotype variants have been identified that are associated with the risk of enterocutaneous fistula development. Immunohistochemical examination of tissues with monoclonal antibodies to α-smooth muscle actin (α-SMA) revealed uneven, focal expression in smooth muscle differentiation cells and fibroblasts. Examination with monoclonal antibodies to Collagen IV there is a moderate positive expression in the basement membrane of blood vessels, in smooth muscle cells of the muscular layer of the vascular wall, in areas of connective tissue.
 Conclusion. Enterocutaneous fistula is 1,5 times more common in carriers of homozygous GG genotype of the tissue inhibitors of metalloproteinase-2 (G303→A) gene and twice less common in heterozygotes GA (25% vs. 40%, p=0,057). Carriers of minor homozygotes of AA genotype in the group with enterocutaneous fistula were not detected, while a similar genotype in the control group was found in 10% of cases. Immunohistochemical examination of small and large intestine tissues with monoclonal antibodies to Collagen IV and α-SMA revealed signs of pathological connective tissue remodeling.