Analysis of genetic risk factors for endometrial hyperplasia in overweight and obese women

DOI

https://dx.doi.org/10.18565/aig.2025.39

Churnosov V.I., Ponomarenko I.V., Ponomarenko M.S., Churnosov M.I.
Belgorod State National Research University, Belgorod, Russia

Objective: To study the association between single nucleotide variants (SNVs) related to body sex hormone levels and the occurrence of endometrial hyperplasia (EH) in overweight and obese women.
Materials and methods: This study included 727 women with a body mass index (BMI) ≥25 kg/m², comprising 324 patients with simple EH (glandular/glandular-cystic forms) and 403 controls. Molecular genetic analysis was conducted on four SNVs associated with sex hormone levels based on data from previous genome-wide association studies (GWAS): NC_000012.12 (ANO2):g.5902324C>A (rs117585797), NC_000016.10 (CHD9):g.52913718A>C (rs117145500), NC_000011.10 (FSHB):g.30193714T>A (rs11031002), and NC_000011.9 (SLC22A24):g.62915346C>A (rs112295236). Associations between SNVs and EH were analyzed using logistic regression.
Results: An association was found between SNV rs11031002 T>A in FSHB and EH across the three genetic models (p=0.001 and pperm=0.001): OR=0.45, 95% CI 0.31–0.66 (allelic model); OR=0.44, 95% CI 0.30–0.64 (additive model); OR=0.45, 95% CI 0.30–0.66 (dominant model). The minor allele A of SNV rs11031002 T>A in FSHB demonstrated a protective effect against disease development (OR<1). Additionally, SNV rs11031002 T>A in FSHB and five polymorphic loci (rs11031005, rs11031006, rs11031010, rs74485684, rs10835638) in linkage disequilibrium with it exhibit significant functionality, influencing the interaction of the FSHB gene promoter with 38 transcription factors and affecting the transcription level of the ARL14EP gene in subcutaneous adipose tissue.
Conclusion: SNV rs11031002 T>A in FSHB is associated with EH risk in overweight and obese women.

Authors' contributions: Churnosov V.I. – literature search and analysis, data summarization, drafting of the manuscript; Ponomarenko I.V. – study conception and design, drafting of the manuscript; Ponomarenko M.S. – statistical analysis; Churnosov M.I. – critical revision, final editing of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: The study was supported by a grant from the Russian Science Foundation No. 25-25-00034,
https://rscf.ru/project/25-25-00034/.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the Belgorod State National Research University.
Patient Consent for Publication: All patients provided informed consent for the publication of their data.
Authors' Data Sharing Statement: The data supporting the findings of this study are available upon request from the corresponding author after approval from the principal investigator.
For citation: Churnosov V.I., Ponomarenko I.V., Ponomarenko M.S., Churnosov M.I. Analysis of
genetic risk factors for endometrial hyperplasia in overweight and obese women.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (5): 58-65 (in Russian)
https://dx.doi.org/10.18565/aig.2025.39

endometrial hyperplasia

single-nucleotide variants

genetic associations

Full text (in Russian)

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Received 19.02.2025

Accepted 30.04.2025

Vladimir I. Churnosov, PhD student at the Department of Biomedical Disciplines, Belgorod State National Research University, 308015, Russia, Belgorod, Pobedy str., 85, +7(4722)30-13-83, vladimirchurnosov@rambler.ru, https://orcid.org/0009-0007-8519-4594
Irina V. Ponomarenko, Dr. Med. Sci., Professor at the Department of Medical and Biological Disciplines, Belgorod State National Research University, 308015, Russia, Belgorod, Pobedy str., 85, +7(4722)30-13-83, ponomarenko_i@bsuedu.ru, https://orcid.org/0000-0002-5652-0166
Marina S. Ponomarenko, PhD student at the Department of Biomedical Disciplines, Belgorod State National Research University, 308015, Russia, Belgorod, Pobedy str., 85, +7(4722)30-13-83, ponomarenkomc@yandex.ru, https://orcid.org/0009-0009-0312-0829
Mikhail I. Churnosov, Dr. Med. Sci., Head of the Department of Medical and Biological Disciplines, Belgorod State National Research University, 308015, Russia, Belgorod, Pobedy str., 85, +7(4722)30-13-83, churnosov@bsuedu.ru, https://orcid.org/0000-0003-1254-6134
Corresponding author: Irina V. Ponomarenko, ponomarenko_i@bsuedu.ru

Analysis of genetic risk factors for endometrial hyperplasia in overweight and obese women

Churnosov V.I., Ponomarenko I.V., Ponomarenko M.S., Churnosov M.I.

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