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One of the factors in the development of uterine fibroids is a genetic predisposition to its occurrence in some women, but the real molecular genetic mechanisms of this phenomenon remain unknown. Aim of the study was the distribution analysis of gene polymorphism of cytokines TNFα, IL-1β, IL-4, IL-6, IL-10, factors of angiogenesis (vascular endothelial growth factor, VEGF) and remodeling of extracellular matrix (metalloproteinases MMP2, MMP3, MMP9), which are associated with their levels. Material and methods. Genotyping was performed by real-time PCR using commercial test systems SYBR GreenI (Litech, Russia) and TaqMan (Syntol, Russia) in accordance with the instructions of the developer. Cytokine content in blood serum was determined by flow cytometry using microspheres coated with monoclonal antibodies to cytokines (Bio-Plex ProTM Human Cytokine 27-plex Assay), according to the instructions for Bio-Plex 200 (Bio-Rad Laboratories, USA).To evaluate the results obtained, in addition to the generally accepted methods of statistical processing for case – control studies, computational methods of bioinformatics were used for comparative analysis of the diagnostic value of various combined genetic traits. Results. It was shown that the maximum odds ratio value of uterine fibroids development are combined genetic traits that include representatives of all four regulatory factors: cytokines with pro-inflammatory activity, cytokines with anti-inflammatory activity, vascular endothelial growth factors and metalloproteinases (p = 0.002). Conclusions. The presented data reveal the real mechanisms of manifestation of the genetic predisposition of individual women to the uterine fibroids development, associated with the presence of polymorphism of certain genes in their genome, which provide features of the structure of cytokine networks with the predominance of certain activities in the regulation of tissue processes in the uterus. In addition to purely scientific interest, these results indicate the real possibility of their clinical application in the form of prognostic criteria with a certain level of prognostic significance.

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.