SAT-153 - Impact of COMT, ESR1, ESR2, AR, and PR Gene Polymorphisms on Hormonal Regulation in Women with Endometriosis

Introduction.
Endometriosis is a hormone-dependent disorder characterized by estrogen predominance, progesterone resistance, and impaired androgen signaling. Genetic polymorphisms in steroid hormone receptors and estrogen-metabolizing enzymes may contribute to these mechanisms.

Objective.
To evaluate the impact of polymorphisms in COMT (c.472G>A), ESR1 (Pvull Polimorphism: c.453-397T>C), ESR2 (g.64233098C>T; c.*39G>A), AR ((CAG)) in repeat), and PR (PGR, PROGINS; g.101062681 C>A; c.1486 G>T) genes in women with endometriosis.

Materials and Methods.
A case–control study included 74 women aged 20–55 years with endometriosis and 72 women aged 20–50 years without the disease. Genomic DNA was analyzed by direct sequencing. Functional activity of receptors and enzyme variants was assessed based on genotypes, and frequencies of alterations were compared between groups.

Results.
Reduced androgen receptor sensitivity was found in 53 patients with endometriosis (71.6%) versus 25 controls (34.7%). A slow COMT variant occurred in 45 patients (60.8%) and 21 controls (29.2%). Increased estrogen receptor α activity was observed in 51 patients (68.9%) versus 19 controls (26.4%), and decreased estrogen receptor β activity in 37 patients (50.0%) versus 17 controls (23.6%). Progesterone receptor activity was reduced in 23 patients (31.1%) and 8 controls (11.1%). All alterations were significantly more frequent in endometriosis. Greater numbers of unfavorable polymorphisms per patient were associated with more severe disease.

Conclusion.
Polymorphisms in COMT, ESR1, ESR2, AR, and PR are linked to impaired hormonal regulation and increased severity of endometriosis. These results highlight the role of genetic factors in disease pathogenesis and the potential for personalized therapeutic strategies.

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