The intestinal sutures insufficiency: factors of risk and prognostication, based on genetic investigations

O. Usenko, Y. Voitiv
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Abstract

Objective. To improve the results of treatment in patients, suffering insufficiency of sutures of intestinal anastomoses, using analysis of rate in the genes polymorphous variants of the matrix metalloproteinase Type 2 (C-1306 →T) and the tissue inhibitor of the matrix metalloproteinase Type 2 (G303 →A), as well as the result of elaboration of genetic diagnosis and prognostication of such complication. Materials and methods. In 32 patients, suffering insufficiency of intestinal sutures, which were treated in Shalimov National Institute of Surgery and Transplantology during 2016 - 2021 yrs, there were conducted the laboratory, genetic, immunohistochemical and statistical investigations. Results. Genetic and statistical analysis for the genes polymorphism of the matrix metalloproteinase Type 2 (C-1306 →T) and the tissue inhibitor of the matrix metalloproteinase Type 2 (G303 →A) have permitted to determine the genotypes variants, associated with risk for the sutures insufficiency occurrence in the hollow gut organs anastomoses. Basing on the data obtained, the prognostication method was elaborated for the sutures insufficiency occurrence in intestinal anastomoses. Such complications are occurred in 1,36 times more frequently in carriers of homozygous СС genotype in gene of the matrix metalloproteinase Type 2 and in two times lesser (5.9%) in carriers the minor homozygotes ТТ, than in the control - 10% (p>0.05). Among the patients with the sutures insufficiency of intestinal anastomoses a statistically significant in 1,6 times more frequent rate of carriers of the homozygous GG gene variant the tissue inhibitor of the matrix metalloproteinase Type 2 was revealed. Carriers of the minor homozygotes АА among the patients with the sutures insufficiency in intestinal anastomoses were absent, while the same genotype was revealed in the control with the 10% (p<0.05) rate. With objective to study the occurrence risk for the sutures insufficiency in intestinal anastomoses in presence of association in the studied genotypes we have analyzed several clinic-laboratory indices. There was revealed the pathogenetic significance of alleles of the genes polymorphic variants of the matrix metalloproteinase Type 2 and the tissue inhibitor of the matrix metalloproteinase Type 2, which were accompanied by hypoproteinemia, high indices of biochemical markers of collagen biodegradation and lowered expression of monoclonal antibodies for α-гладкоmuscular actin and collagen IV, and, finally. have evolved as the risk factors for development of the sutures insufficiency in intestinal anastomoses. Conclusion. The method proposed consists of genetic investigation of the genes polymorphism of the matrix metalloproteinase Type 2 (C-1306 →T) and of the tissue inhibitor of the matrix metalloproteinase Type 2 (G303 →A). It permits to prognosticate the probability of the sutures insufficiency development in intestinal anastomoses, and, basing on this, to improve the choice of the patients’ treatment tactic.
肠缝合线不全:风险因素和预后,基于遗传调查
目标。通过对基质金属蛋白酶2型(C-1306→T)和基质金属蛋白酶2型组织抑制剂(G303→A)基因多态性变异率的分析,以及对该类并发症的遗传诊断和预后的阐述,以提高肠吻合口缝合不全患者的治疗效果。材料和方法。对2016 - 2021年沙里莫夫国立外科与移植研究所收治的32例肠缝合线不全患者进行了实验室、遗传学、免疫组化和统计学调查。结果。通过对基质金属蛋白酶2型(C-1306→T)和基质金属蛋白酶2型组织抑制剂(G303→A)基因多态性的遗传和统计分析,确定了与空心肠器官吻合口发生缝合线不全风险相关的基因型变异。在此基础上,阐述了肠吻合口发生缝合线不全的预后方法。基质金属蛋白酶2型基因纯合子СС基因型携带者的并发症发生率为对照组的1.36倍,次纯合子ТТ基因型携带者的并发症发生率为对照组的5.9%,为对照组的2倍(p>0.05)。在肠吻合口缝合功能不全的患者中,纯合GG基因变异携带者的出现频率是前者的1.6倍,有统计学意义,显示基质金属蛋白酶2型的组织抑制剂。小肠吻合口缝合不全患者中未出现少量纯合子АА携带者,对照组中出现少量纯合子АА携带者,比例为10% (p<0.05)。为了探讨肠吻合口缝合线不全的发生风险与所研究的基因型存在相关性,我们分析了几种临床-实验室指标。基质金属蛋白酶2型基因多态性变异和基质金属蛋白酶2型组织抑制剂等位基因的致病意义,伴有低蛋白血症、胶原生物降解生化标志物指数增高、α-гладкоmuscular肌动蛋白单克隆抗体和IV型胶原单克隆抗体表达降低;已演变为肠吻合口缝合线不全的危险因素。结论。该方法包括基质金属蛋白酶2型(C-1306→T)和基质金属蛋白酶2型组织抑制剂(G303→A)基因多态性的遗传研究。它可以预测肠吻合口缝合线发育不全的概率,并在此基础上改善患者治疗策略的选择。
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