The BAIAP2L1 gene variant as a risk factor for the development of genital endometriosis in combination with endometrial hyperplasia

DOI

https://dx.doi.org/10.18565/aig.2025.71

Ponomareva T.A., Altukhova O.B., Ponomarenko I.V., Churnosov M.I.
1) Belgorod National Research University, Belgorod, Russia; 2) St.Ioasaph Belgorod Regional Clinical Hospital, Belgorod, Russia

Objective: To investigate the association between single nucleotide variants (SNVs) and the occurrence of genital endometriosis combined with endometrial hyperplasia in the Russian population in the following genes: NC_000017.11 (SHBG):g.7618597G>T (rs12150660), NC_000001.11 (PRMT6):g.107003753A>G (rs17496332), NC_000007.14 (BAIAP2L1):g.98364050T>A (rs3779195), NC_000012.12 (SLCO1B1):g.21178615T>C (rs4149056), and NC_000015.10 (NR2F2):g.96165062T>C (rs8023580).
Materials and methods: GWAS-significant single nucleotide variants (SNVs) associated with sex hormone-binding globulin (SHBG) levels were genotyped in 286 patients with genital endometriosis, including 183 patients with both genital endometriosis and endometrial hyperplasia and 103 patients with isolated genital endometriosis (control group). Logistic regression was used to assess the association between GWAS-significant SNVs linked to SHBG levels and the development of genital endometriosis in combination with endometrial hyperplasia. Allelic, additive, recessive, and dominant models were applied using the gPLINK software.
Results: The A allele of the BAIAP2L1 (rs3779195) gene was identified as a risk factor for the development of endometriosis in combination with endometrial hyperplasia (OR=2.85; 95% CI 1.36–5.97; pperm=0.006 for the additive model; OR=1.91; 95% CI 1.15–3.17; pperm=0.014 for the allelic model; OR=2.72; 95% CI 1.26–5.88; pperm=0.012 for the dominant model). The rs3779195 locus is located in the intronic region of the BAIAP2L1 gene, characterizes DNA interaction with the Foxp1 transcription factor, and is in linkage disequilibrium with 20 SNV, four of which (rs6950023, rs6967728, rs77032872, and rs3779196) exhibit significant regulatory potential.
Conclusion: The A allele of BAIAP2L1 (rs3779195) is associated with an increased risk of genital endometriosis in combination with endometrial hyperplasia.

Authors' contributions: Ponomareva T.A. – conducting the study, summarizing the data, drafting of the manuscript; Ponomarenko I.V. – editing of the manuscript; Altukhova O.B. – conducting the study, conception and plan of the article; Churnosov M.I. – reviewing, final editing of the manuscript.
Conflicts of interest: The authors have no conflicts of interest to declare.
Funding: There was no funding for this study.
Ethical Approval: The study was reviewed and approved by the Research Ethics Committee of the St. Ioasaph Belgorod Regional Clinical Hospital.
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: Ponomareva T.A., Altukhova O.B., Ponomarenko I.V., Churnosov M.I.
The BAIAP2L1 gene variant as a risk factor for the development of genital endometriosis
in combination with endometrial hyperplasia.
Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2025; (7): 84-91 (in Russian)
https://dx.doi.org/10.18565/aig.2025.71

genital endometriosis

single nucleotide variant (SNV)

associations

SHBG

candidate genes

risk factor

endometrial hyperplasia

Full text (in Russian)

Crump J., Suker A., White L. Endometriosis: a review of recent evidence and guidelines. Aust. J. Gen. Pract. 2024; 53(1-2): 11-8. https://dx.doi.org/10.31128/AJGP/04-23-6805
Wang P.H., Yang S.T., Chang W.H., Liu C.H., Lee F.K., Lee W.L. Endometriosis: part I. Basic concept. Taiwan. J. Obstet. Gynecol. 2022; 61(6): 927-34. https://dx.doi.org/10.1016/j.tjog.2022.08.002
Smolarz B., Szyłło K., Romanowicz H. Endometriosis: epidemiology, classification, pathogenesis, treatment and genetics (review of Literature). Int. J. Mol. Sci. 2021; 22(19): 10554. https://dx.doi.org/10.3390/ijms221910554
Koninckx P.R., Fernandes R., Ussia A., Schindler L., Wattiez A., Al-Suwaidi S. et al. Pathogenesis based diagnosis and treatment of endometriosis. Front. Endocrinol. (Lausanne). 2021; 12: 745548. https://dx.doi.org/10.3389/fendo.2021.745548
Zondervan K.T., Becker C.M., Missmer S.A. Endometriosis. N. Engl. J. Med. 2020; 382(13): 1244-56. https://dx.doi.org/10.1056/NEJMra1810764
Ponomarenko M.S., Reshetnikov E.A., Churnosova M.M., Reshetnikova Y.N., Churnosov V.I., Ponomarenko I.V. Comorbidity and syntropy of benign proliferative diseases of the female reproductive system: non-genetic, genetic, and epigenetic factors (review). Research Results in Biomedicine. 2023; 9(4): 544-56. https://dx.doi.org/10.18413/2658-6533-2023-9-4-0-9
Пономарева Т.А., Алтухова О.Б., Пономаренко И.В., Чурносов М.И. Современные представления о механизмах развития и факторах риска эндометриоза. Акушерство и гинекология. 2024; 7: 12-20. [Ponomareva T.A., Altukhova O.B., Ponomarenko I.V., Churnosov M.I. Novel concepts in the pathogenesis and risk factors of endometriosis. Obstetrics and Gynecology. 2024; (7): 12-20 (in Russian)]. https://dx.doi.org/10.18565/aig.2024.110
Пономаренко И.В., Полоников А.В., Верзилина И.Н., Чурносов М.И. Молекулярно-генетические детерминанты развития эндометриоза. Вопросы гинекологии, акушерства и перинатологии. 2019; 18(1): 82-6 [Ponomarenko I.V., Polonikov A.V., Verzilina I.N., Churnosov M.I. Molecular-genetic determinants of the development of endometriosis. Gynecology, Obstetrics, and Perinatology. 2019; 18(1): 82-6 (in Russian)]. https://dx.doi.org/10.20953/1726-1678-2019-1-82-86
Signorile P.G., Baldi A., Viceconte R., Ronchi A., Montella M. Pathogenesis of endometriosis: focus on adenogenesis-related factors. In Vivo. 2023; 37(5): 1922-30. https://dx.doi.org/10.21873/invivo.13288
Adilbayeva A., Kunz J. Pathogenesis of endometriosis and endometriosis-associated cancers. Int. J. Mol. Sci. 2024; 25(14): 7624. https://dx.doi.org/10.3390/ijms25147624
Kim H., Kim H.J., Ahn H.S. Does endometriosis increase the risks of endometrial hyperplasia and endometrial cancer? Gynecol. Oncol. 2023; 169: 147-53. https://dx.doi.org/10.1016/j.ygyno.2022.06.021
Пономаренко И.В., Полоников А.В., Чурносов М.И. Молекулярные механизмы и факторы риска развития эндометриоза. Акушерство и гинекология. 2019; 3: 26-31. [Ponomarenko I.V., Polonikov A.V., Churnosov M.I. Molecular mechanisms of and risk factors for endometriosis. Obstetrics and Gynecology. 2019; (3): 26-31 (in Russian)]. https://dx.doi.org/10.18565/aig.2019.3.26-31
Радзинский В.Е., Алтухова О.Б. Молекулярно-генетические детерминанты бесплодия при генитальном эндометриозе. Научные результаты биомедицинских исследований. 2018; 4(3): 28-37. [Radzinsky V.E., Altukhova O.B. Molecular-genetic determinants of infertility in genital endometriosis. Research Results in Biomedicine. 2018; 4(3): 28-37 (in Russian)]. https://dx.doi.org/10.18413/2313-8955-2018-4-3-0-3
Андреев А.Е., Клейменова Т.С., Дробинцева А.О., Полякова В.О., Кветной И.М. Сигнальные молекулы, вовлеченные в образование новых нервных окончаний при эндометриозе (обзор). Научные результаты биомедицинских исследований. 2019; 5(1): 94-107. [Andreev A.E., Kleimenova T.S., Drobintseva A.O., Polyakova V.O., Kvetnoy I.M. Signal molecules involved in formation of new nerve endings in endometriosis (review). Research Results in Biomedicine. 2019; 5(1): 94-107 (in Russian)]. https://dx.doi.org/10.18413/2313-8955-2019-5-1-0-7
Narinx N., David K., Walravens J., Vermeersch P., Claessens F., Fiers T. et al. Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology. Cell. Mol. Life Sci. 2022; 79(11): 543. https://dx.doi.org/10.1007/s00018-022-04562-1
Simons P.I.H.G., Valkenburg O., Stehouwer C.D.A., Brouwers M.C.G.J. Sex hormone-binding globulin: biomarker and hepatokine? Trends Endocrinol. Metab. 2021; 32(8): 544-53. https://dx.doi.org/10.1016/j.tem.2021.05.002
Coviello A.D., Haring R., Wellons M., Vaidya D., Lehtimäki T., Keildson S. et al. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple loci implicated in sex steroid hormone regulation. PLOS Genet. 2012; 8(7): e1002805. https://dx.doi.org/10.1371/journal.pgen.1002805
Harrison S., Davies N. M., Howe L. D., Hughes A. Testosterone and socioeconomic position: mendelian randomization in 306,248 men and women in UK Biobank. Sci. Adv. 2021; 7(31): eabf8257. https://dx.doi.org/10.1126/sciadv.abf8257
Пономарева Т.А., Алтухова О.Б., Пономаренко И.В., Чурносов М.И. Роль генетических факторов в формировании эндометриоидных поражений. Акушерство, гинекология и репродукция. 2023; 17(4): 443-54 [Ponomareva T.A., Altukhova O.B., Ponomarenko I.V., Churnosov M.I. The role of genetic factors in developing endometrioid lesions. Obstetrics, Gynecology and Reproduction. 2023; 17(4): 443-54 (in Russian)]. https://dx.doi.org/110.17749/2313-7347/ob.gyn.rep.2023.434
Golovchenko I., Aizikovich B., Golovchenko O., Reshetnikov E., Churnosova M., Aristova I. et al. Sex hormone candidate gene polymorphisms are associated with endometriosis. Int. J. Mol. Sci. 2022; 23(22): 13691. https://dx.doi.org/10.3390/ijms232213691
HaploReg v4.2. https://pubs.broadinstitute.org/mammals/haploreg/haploreg.php (accessed 02.04.2025).
GTExPortal. https://gtexportal.org/home (accessed 24.06.2025).
PLINK v1.07. https://zzz.bwh.harvard.edu/plink/ (accessed 02.04.2025).
Ruth K.S., Day F.R., Tyrrell J., Thompson D.J., Wood A.R., Mahajan A. et al. Using human genetics to understand the disease impacts of testosterone in men and women. Nat. Med. 2020; 26(2): 252-8. https://dx.doi.org/10.1038/s41591-020-0751-5
Пасенов К.Н. Особенности ассоциаций SHBG-связанных генов с раком молочной железы у женщин в зависимости от наличия наследственной отягощенности и мутаций в генах BRCA1/CHEK2. Научные результаты биомедицинских исследований. 2024; 10(1): 69-88. [Pasenov K.N. Features of associations of SHBG-related genes with breast cancer in women, depending on hereditary burden and mutations in BRCA1/CHEK2 genes. Research Results in Biomedicine. 2024; 10(1): 69-88 (in Russian)]. https://dx.doi.org/10.18413/2658-6533-2024-10-1-0-4
Головченко И.О. Генетические детерминанты уровня половых гормонов у больных эндометриозом. Научные результаты биомедицинских исследований. 2023; 9(1): 5-21. [Golovchenko I.O. Genetic determinants of sex hormone levels in endometriosis patients. Research Results in Biomedicine. 2023; 9(1): 5-21 (in Russian)]. https://dx.doi.org/10.18413/2658-6533-2023-9-1-0-1
Yuan S., Wang L., Sun J., Yu L., Zhou X., Yang J. et al. Genetically predicted sex hormone levels and health outcomes: phenome-wide Mendelian randomization investigation. Int. J. Epidemiol. 2022; 51(6): 1931-42. https://dx.doi.org/10.1093/ije/dyac036
Пономарева Т.А. Генетические варианты глобулина, связывающего половые гормоны, и гормональный профиль больных генитальным эндометриозом. Научные результаты биомедицинских исследований. 2025; 11(1): 75-90. [Ponomareva T.A. Genetic variants of sex hormone-binding globulin and hormonal profile in patients with genital endometriosis. Research Results in Biomedicine. 2025; 11(1): 75-90 (in Russian)]. https://dx.doi.org/10.18413/2658-6533-2025-11-1-0-4
Nees L.K., Heublein S., Steinmacher S., Juhasz-Böss I., Brucker S., Tempfer C.B. et al. Endometrial hyperplasia as a risk factor of endometrial cancer. Arch. Gynecol. Obstet. 2022; 306(2): 407-21. https://dx.doi.org/10.1007/s00404-021-06380-5

Received 13.03.2025

Accepted 01.07.2025

Tatyana A. Ponomareva, PhD student, Department of Medical and Biological Disciplines, Belgorod National Research University, 85 Pobedy str., 308015, Belgorod, Russia; Obstetrician-Gynecologist, Belgorod Regional Clinical Hospital of St. Joasaph, 8/9 Nekrasov str., 308007, Belgorod, Russia, rybaarbusova@icloud.com,
https://orcid.org/0009-0007-8533-9319
Oksana B. Altukhova, Dr. Med. Sci., Associate Professor, Head of the Department of Obstetrics and Gynecology, Belgorod National Research University, 85 Pobedy str., 308015, Belgorod, Russia; Head of Gynecological Department, Belgorod Regional Clinical Hospital of St. Joasaph, 8/9 Nekrasov str., 308007, Belgorod, Russia,
altuhova_o@bsuedu.ru, https://orcid.org/0000-0003-4674-8797
Irina V. Ponomarenko, Dr. Med. Sci., Associate Professor, Department of Medical and Biological Disciplines, Belgorod National Research University, 85 Pobedy str.,
308015, Belgorod, Russia, ponomarenko_i@bsuedu.ru, https://orcid.org/0000-0002-5652-0166
Mikhail I. Churnosov, Dr. Med. Sci., Professor, Head of the Department of Medical and Biological Disciplines, Belgorod National Research University, 85 Pobedy str.,
308015, Belgorod, Russia, churnosov@bsuedu.ru, https://orcid.org/ 0000-0003-1254-6134
Corresponding author: Tatyana A. Ponomareva, rybaarbusova@icloud.com

The BAIAP2L1 gene variant as a risk factor for the development of genital endometriosis in combination with endometrial hyperplasia

Ponomareva T.A., Altukhova O.B., Ponomarenko I.V., Churnosov M.I.

Keywords

References

About the Authors

Similar Articles