Features of Matrix Metalloproteinases MMP2, MMP3, and MMP9 of Regulatory-Region Polymorphism in Patients with Uterine Fibroids

Q4 Biochemistry, Genetics and Molecular Biology

Cell and Tissue Biology Pub Date : 2023-12-11 DOI:10.1134/s1990519x23060135

A. V. Shevchenko, V. F. Prokof’ev, V. I. Konenkov, Yu. S. Timofeeva, E. G. Koroleva, I. O. Marinkin, S. V. Aidagulova

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Abstract

Dysregulation of the extracellular matrix components synthesis contributes to the formation and growth of uterine fibroids. Changes of collagen metabolism in connective tissue may be associated with polymorphism of matrix metalloproteinase (MMP) genes. The aim of the study was to analyze of the association of regulatory regions of matrix metalloproteinase MMP2 (rs243865), MMP3 (rs3025058), and MMP9 (rs3918242) genes with the development of leiomyoma, its histological form, and several concomitant gynecological diseases. A clinical study of 69 patients (23–54 years old) with myomas was conducted. According to the anamnesis, 57.9% of patients had given birth, 46.4% of women had had an artificial interruption of pregnancy, and 15.9% of women had had endometriosis. In histological examination, in 48.14% of cases, the nodes corresponded to the phenotype of simple fibroids with a large proportion of fibrous tissue, while 51.6% corresponded to the phenotype of proliferating fibroids. The comparison group is represented by a random population sample of women from Western Siberia. A total of 183 women without pronounced gynecological diseases were examined. MMP2-1306 C/T polymorphism was analyzed by TaqMan, MMP3-1171 5A/6A, and MMP9-1562 C/T by restriction fragment length polymorphism method. The genotype frequencies of the analyzed genes did not significantly differ between the groups. The complex genotype MMP2-1306CC:MMP3-11715A6A:MMP9-1562CT was decreased in women with myoma relative to the persons of the comparison group. In endometriosis patients, the MMP9-1562CC genotype was reduced and heterozygosity was increased relative to patients without endometriosis. The frequency of the MMP2-1306CC:MMP9-1562CT complex genotype is significantly higher in women who gave birth than in women who did not give birth. Differences in frequencies of complex genotypes between histological variants of leiomyoma were revealed. The results of the study show the significance of polymorphism effect of the regulatory regions of the MMP genes in the development of leiomyoma and nature of disease progression.

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子宫肌瘤患者基质金属蛋白酶 MMP2、MMP3 和 MMP9 的调节区多态性特征

摘要细胞外基质成分合成失调是子宫肌瘤形成和生长的原因之一。结缔组织中胶原蛋白代谢的变化可能与基质金属蛋白酶（MMP）基因的多态性有关。该研究旨在分析基质金属蛋白酶 MMP2（rs243865）、MMP3（rs3025058）和 MMP9（rs3918242）基因的调控区域与子宫肌瘤的发生、组织学形态以及几种并发妇科疾病的关系。研究人员对 69 名子宫肌瘤患者（23-54 岁）进行了临床研究。根据病史，57.9%的患者曾经生育，46.4%的妇女曾经人工中止妊娠，15.9%的妇女曾经患有子宫内膜异位症。在组织学检查中，48.14%的病例的结节符合单纯纤维肌瘤的表型，其中纤维组织占很大比例，而 51.6%的病例则符合增生性纤维肌瘤的表型。对比组的代表是西西伯利亚的随机人口抽样妇女。共对 183 名无明显妇科疾病的妇女进行了检查。用 TaqMan 方法分析了 MMP2-1306 C/T 多态性，用限制性片段长度多态性方法分析了 MMP3-1171 5A/6A 和 MMP9-1562 C/T。各组间分析基因的基因型频率无明显差异。与对比组相比，肌瘤妇女的复合基因型MMP2-1306CC:MMP3-11715A6A:MMP9-1562CT有所减少。在子宫内膜异位症患者中，与无子宫内膜异位症的患者相比，MMP9-1562CC基因型减少，杂合度增加。在生育过的妇女中，MMP2-1306CC:MMP9-1562CT复合基因型的频率明显高于未生育过的妇女。研究还发现了不同组织学变异的子宫肌瘤复合基因型的频率差异。研究结果表明，MMP 基因调控区的多态性效应对子宫肌瘤的发展和疾病进展的性质具有重要意义。

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来源期刊

Cell and Tissue Biology Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

0.80

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0.00%

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期刊介绍： The journal publishes papers on vast aspects of cell research, including morphology, biochemistry, biophysics, genetics, molecular biology, immunology. The journal accepts original experimental studies, theoretical articles suggesting novel principles and approaches, presentations of new hypotheses, reviews highlighting major developments in cell biology, discussions. The main objective of the journal is to provide a competent representation and integration of research made on cells (animal and plant cells, both in vivo and in cell culture) offering insight into the structure and functions of live cells as a whole. Characteristically, the journal publishes articles on biology of free-living and parasitic protists, which, unlike Metazoa, are eukaryotic organisms at the cellular level of organization.