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

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Abstract

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.

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About the authors

Vladimir I. Churnosov

Belgorod State National Research University

Email: vladimirchurnosov@rambler.ru
ORCID iD: 0009-0007-8519-4594

PhD student at the Department of Biomedical Disciplines

Russian Federation, Belgorod

Irina V. Ponomarenko

Belgorod State National Research University

Author for correspondence.
Email: ponomarenko_i@bsuedu.ru
ORCID iD: 0000-0002-5652-0166

Dr. Med. Sci., Professor at the Department of Medical and Biological Disciplines

Russian Federation, Belgorod

Marina S. Ponomarenko

Belgorod State National Research University

Email: ponomarenkomc@yandex.ru
ORCID iD: 0009-0009-0312-0829

PhD student at the Department of Biomedical Disciplines

Russian Federation, Belgorod

Mikhail I. Churnosov

Belgorod State National Research University

Email: churnosov@bsuedu.ru
ORCID iD: 0000-0003-1254-6134

Dr. Med. Sci., Head of the Department of Medical and Biological Disciplines

Russian Federation, Belgorod

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