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

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.