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

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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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Funding

This study was performed within the framework of a state order to the Research Institute of Clinical and Experimental Lymрhology, Branch of the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences (no. 122022800132-1), and a state order to Novosibirsk State Medical University, Ministry of Health of the Russian Federation (no. 121021700349-8).

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Authors and Affiliations

  1. Research Institute of Clinical and Experimental Lymрhology, Branch of the Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, 630117, Novosibirsk, Russia

    A. V. Shevchenko, V. F. Prokof’ev & V. I. Konenkov

  2. Novosibirsk State Medical University, Ministry of Health of the Russian Federation, 630091, Novosibirsk, Russia

    Yu. S. Timofeeva, I. O. Marinkin & S. V. Aidagulova

  3. Avicenna Mother and Child Multifunctional Clinical Hospital, 630099, Novosibirsk, Russia

    Yu. S. Timofeeva & E. G. Koroleva

Authors
  1. A. V. Shevchenko
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  2. V. F. Prokof’ev
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  3. V. I. Konenkov
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  4. Yu. S. Timofeeva
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  5. E. G. Koroleva
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  6. I. O. Marinkin
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  7. S. V. Aidagulova
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Correspondence to A. V. Shevchenko.

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Conflict of interest. The authors declare that they have no conflicts of interest.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee of the Research Institute of Clinical and Experimental Lymрhology, Branch of the Institute of Cytology and Genetics, Novosibirsk State Regional Clinical Hospital (protocol no. 3 of November 28, 2013), and Novosibirsk State Medical University (protocol no. 107 of May 31, 2018). Informed consent was obtained from all individual participants involved in the study.

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Translated by M. Novikova

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Shevchenko, A.V., Prokof’ev, V.F., Konenkov, V.I. et al. Features of Matrix Metalloproteinases MMP2, MMP3, and MMP9 of Regulatory-Region Polymorphism in Patients with Uterine Fibroids. Cell Tiss. Biol. 17, 699–705 (2023). https://doi.org/10.1134/S1990519X23060135

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  • DOI: https://doi.org/10.1134/S1990519X23060135

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