GENES OF ESTROGEN AND PROGESTERONE RECEPTORS AND CHARACTERISTICS OF UTERINE DAMAGE IN MYOMA

Relevance: A uterine myoma is a hormone-dependent tumor composed of muscle and connective tissue elements. It occupies a special place in the spectrum of tumors affecting the female reproductive system, accounting for 10–20% of all gynecological pathologies, and is diagnosed in 10–30% of women of reproductive age. One important aspect of the pathogenesis of uterine fibroids is the imbalance between progesterone and estrogen levels, which creates conditions conducive to the rapid growth of fibroid nodules. Polymorphisms in the genes of estrogen and progesterone receptors may influence their expression and, therefore, be significant in the pathophysiology of large uterine myomas. Objective: To investigate the associations between combined polymorphic variants of estrogen and progesterone receptor genes and the development of large uterine myomas. Materials and methods: A total of patients (n=380) diagnosed with uterine fibroids were divided into three groups based on the size of the largest nodule. Five polymorphic loci of estrogen and progesterone receptors were selected for the study: rs2234693 ESR1 c453-397T>C, rs3798577 ESR1 c.1029T>C, rs9340799 ESR1 c.453-351A>G, rs484389 PGR c.38T>C, and rs1042838 PGR c.1415-11113G>T. The analysis was performed by polymerase chain reaction (PCR) on a CFX-96 Real-Time System thermal cycler. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to determine associations. The APSampler program (https://sourceforge.net/ projects/apsampler/) was used to evaluate the associations of allele and genotype combinations of the analyzed genes with the occurrence of large myomas. The online programs HaploReg and Gtex Portal were used to assess the functional effects of SNPs associated with the formation of large myomas. Results: This study demonstrated a significant role of ESR1 rs3798577, ESR1 rs9340799, PGR rs484389, and PGR rs1042838 in the characteristics of uterine fibroids. A combination of polymorphic variants C rs3798577 ESR1 and AA rs9340799 ESR1 should be considered a risk factor for the development of large uterine fibroids (OR = 2.30-2.42), while a combination of markers GG rs1042838 PGR, C rs484389 PGR, and G rs9340799 ESR1 should be regarded as a protective factor against the formation of large nodules (OR=0.27–0.28). Conclusion: The polymorphic loci ESR1 rs3798577, ESR1 rs9340799, PGR rs484389, and PGR rs1042838 were associated with the development of large uterine fibroids. The combinations of allelic variants of estrogen and progesterone receptor genes identified for the first time, which are associated with an increased risk of developing large uterine fibroids, underscores the importance of the interaction of polymorphic gene variants in the formation of this pathology. These findings may have practical applications in identifying risk groups for preventive measures. © 2025 Elsevier B.V., All rights reserved.