子宫肌瘤患者基质金属蛋白酶MMP2、MMP3、MMP9基因调控区多态性特征

Q4 Biochemistry, Genetics and Molecular Biology Sibirskii nauchnyi meditsinskii zhurnal Pub Date : 2023-04-28 DOI:10.18699/ssmj20230209
A. Shevchenko, V. F. Prokofev, V. Konenkov, Yu. S. Timofeeva, E. Koroleva, I. Marinkin, S. Aidagulova
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引用次数: 0

摘要

破坏细胞外基质成分合成调节有助于子宫肌瘤(MM)的形成和生长。结缔组织中胶原代谢的变化可能与基质金属蛋白酶(MMP)基因多态性有关。本研究旨在分析基质金属蛋白酶基因MMP2 (rs243865)、MMP3 (rs3025058)、MMP9 (rs3918242)调控区域与子宫肌瘤的发生、组织学形态及多种妇科疾病的关系。材料和方法。对69例(23 ~ 54岁)子宫肌瘤患者进行临床研究。根据记忆,57.9%的患者分娩,46.4%的女性人工终止妊娠,15.9%的女性子宫内膜异位症。在组织学检查中,48.14%的淋巴结符合单纯性纤维瘤的表型,其中纤维组织占很大比例,51.6%的淋巴结符合增殖性纤维瘤的表型。对照组是来自西伯利亚西部的随机抽样妇女,检查了183名没有明显妇科疾病的妇女。采用TaqMan分析MMP2-1306 C/T多态性,采用限制性片段长度多态性法分析MMP3-1171 5A/6A, MMP9-1562 C/T多态性。结果。所分析基因的基因型频率在组间无显著差异。复合基因型MMP2-1306CC:MMP3-11715A6A:MMP9-1562CT在子宫肌瘤患者中较对照组降低。在子宫内膜异位症患者中,MMP9-1562CC基因型相对于无子宫内膜异位症患者减少,杂合度增加。生育妇女MMP2-1306CC:MMP9-1562CT复合基因型的频率明显高于未生育妇女。揭示了子宫肌瘤组织学变异的复杂基因型差异。结论。本研究结果表明MMP基因调控区域的多态性效应在子宫肌瘤的发展和病程性质中具有重要意义。
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Features of matrix metalloproteinases MMP2, MMP3, MMP9 genes regulatory region polymorphism in patients with uterine fbroids
Violation of the extracellular matrix components synthesis regulation contributes to the formation and growth of uterine fbroids (MM). Changes of collagen metabolism in connective tissue may be associated with polymorphism of matrix metalloproteinase (MMP) genes. Aim of the study was to analyze of the association of regulatory regions of matrix metalloproteinase genes MMP2 (rs243865), MMP3 (rs3025058), MMP9 (rs3918242) with the development of uterine myoma, its histological form, several concomitant gynecological diseases. Material and methods. The clinical study of 69 patients (23–54 years old) with uterine myoma was conducted. According to the anamnesis, 57.9 % of patients had childbirth, 46.4 % of women had an artifcial termination of pregnancy, and 15.9 % of women had endometriosis. In histological examination, in 48.14 % the nodes corresponded to the phenotype of simple fbroids with a large proportion of fbrous tissue, 51.6 % with the phenotype of proliferating fbroids. The comparison group is represented by a random population sample of women from Western Siberia. 183 women without pronounced gynecological pathologies were examined. MMP2-1306 C/T polymorphism was analyzed by TaqMan, MMP3-1171 5A/6A, MMP9-1562 C/T by restriction fragment length polymorphism method. Results. The genotype frequencies of the analyzed genes did not signifcantly differ between the groups. The complex genotype MMP2-1306CC:MMP3-11715A6A:MMP9-1562CT was decreased in women with uterine myoma relative to the persons of the comparison group. In endometriosis patients MMP9-1562CC genotype was reduced and heterozygosity was increased relative to patients without endometriosis. The frequency of MMP2-1306CC:MMP9-1562CT complex genotype is signifcantly higher in women who gave birth than in women who did not give birth. Complex genotypes differences between histological variants of uterine myoma were revealed. Conclusions. The results of the study show the signifcance of polymorphism effect of the regulatory regions of the MMP genes in the development and nature of the course of uterine myoma.
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