Association of ESR2 rs4986938 polymorphism with the development of endometrial hyperplasia

Ponomarenko I.V., Polonikov A.V., Churnosov M.I.

1) Belgorod State National Research University, Belgorod, Russia; 2) Kursk State Medical University, Ministry of Health of Russia, Kursk, Russia
Objective: to study associations of ESR1 rs3020394 and rs1884051 and ESR2 rs4986938 polymorphisms with the development of endometrial hyperplasia.
Subjects and methods. The study included 1501 women: 520 patients with simple endometrial hyperplasia and 981 control-group individuals. ESR1 rs3020394 and rs1884051 and ESR2 rs4986938 polymorphisms were genotyped.
Results. ESR2 rs4986938 polymorphism was established to be associated with the development of endometrial hyperplasia. The A/A genotype is a risk factor for the development of the disease (OR = 1.43). ESR2 rs4986938 polymorphism had substantial regulatory effects (it was located in the region of histones that marked enhancers in 17 different organs and tissues, at the DNase I hypersensitive sites in 6 tissues, in the DNA regulatory motif regions that were binding sites of 5 transcriptional factors (CTCF_known1, Nr2f2, Pax-6_1, Pax-8_1, and RAR) and affected the expression of the ESR2, SYNE2, and MTHFD1 genes.
Conclusion. ESR2 rs4986938 polymorphism is associated with the development of endometrial hyperplasia.

Keywords

endometrial hyperplasia
polymorphism

References

  1. Киселев В.И., Сидорова И.С., Унанян А.Л., Муйжнек Е.Л. Гиперпластические процессы органов женской репродуктивной системы: теория и практика. М.: МЕДПРАКТИКА-М; 2010. 468с. [Kiselev V.I., Sidorova I.S., Unanyan A.L., Muizhnek E.L. Hyperplastic processes of the organs of the female reproductive system: theory and practice. M .: MEDPRAKTIKA-M; 2010. 468p. (in Russian)].
  2. Адамян Л.В., ред. Cочетанные доброкачественные опухоли и гиперпластические процессы матки (миома, аденомиоз, гиперплазия эндометрия). Проект клинических рекомендаций по ведению больных. Адамян Л.В., Андреева Е.Н., Аполихина И.А., Балан В.Е., Беженарь В.Ф., Геворкян М.А. и др. М.: Изд-во Научного центра акушерства, гинекологии и перинатологии им. В. И. Кулакова; 2015. 92с. [Adamyan L.V., ed. Combined benign tumors and hyperplastic processes of the uterus (fibroids, adenomyosis, endometrial hyperplasia). Draft clinical guidelines for the management of patients. Adamyan L.V., Andreeva E.N., Apolikhina I.A., Balan V.E., Bezhenar V.F., Gevorkyan M.A. and others. M .: Publishing house of the Scientific Center for Obstetrics, Gynecology and Perinatology them. V.I. Kulakov; 2015. 92p. (in Russian)].
  3. Chandra V., Kim J.J., Benbrook D.M., Dwivedi A., Rai R. Therapeutic options for management of endometrial hyperplasia. Journal of Gynecologic Oncology. 2016;27(1):e8. doi:10.3802/jgo.2016.27.e8.
  4. Kadirogullari P., Atalay C.R., Ozdemir O., Erkan M. Sari Prevalence of Co-existing Endometrial Carcinoma in Patients with Preoperative Diagnosis of Endometrial Hyperplasia. J. Clin. Diagn. Res. 2015;9(10):QC10–QC14.
  5. Ørbo A., Arnes M., Vereide A., Straume B. Relapse risk of endometrial hyperplasia after treatment with the levonorgestrel‐impregnated intrauterine system or oral progestogens. Bjog. 2016;123(9):1512-1519. doi:10.1111/1471-0528.13763.
  6. Чернуха Г.Е., Асатурова А.В., Иванов И.А., Думановская М.Р. Структура патологии эндометрия в различные возрастные периоды. Акушерство и гинекология. 2018; 8: 129-34. https://dx.doi.org/10.18565/aig.2018.8.129-134. [Chernukha G.E., Asaturova A.V., Ivanov I.A., Dumanovskaya M.R. The structure of the pathology of the endometrium at different ages. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; 8: 129-34. https://dx.doi.org/10.18565/aig.2018.8.129-134. (in Russian)].
  7. Пономаренко И.В., Полоников А.В., Чурносов М.И. Гиперпластические процессы эндометрия: этиопатогенез, факторы риска, полиморфизм генов-кандидатов. Акушерство и гинекология. 2019; 1: 13-18. [Ponomarenko I.V., Polonikov A.V., Churnosov M.I. Endometrial hyperplastic processes: etiopathogenesis, risk factors, polymorphism of candidate genes. Akusherstvo I Ginekologiya/Obstetrics and Gynecology. 2019; 1: 13-18. (in Russian)].
  8. Рудых Н.А., Сиротина С.С. Генетические соотношения русских и украинских популяций Белгородской области. Научный результат. Медицина и фармация. 2015;1(3):72-79. [Rudyh N.A., Sirotina S.S. Genetic interrelations of Russian and Ukrainian populations of Belgorod region]. Research Result. Medicine and Pharmacy. 2015;1(3):72-79. (in Russian)]. DOI: 10.18413/2313-8955-2015-1-3-72-79
  9. Пономаренко И.В. Отбор полиморфных локусов для анализа ассоциаций при генетико-эпидемиологических исследованиях. Научный результат. Медицина и фармация. 2018;4(2):40-54. [Ponomarenko I.V. Selection of polymorphic loci for association analysis in genetic-epidemiological studies. Research Result. Medicine and Pharmacy. 2018;4(2):40-54. (in Russian)]. DOI: 10.18413/2313-8955-2018-4-2-0-5
  10. Ward L.D., Kellis M. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Res. 2016;44:877–881.
  11. Пономаренко И.В., Решетников Е.А., Полоников А.В., Чурносов М.И. Полиморфный локус rs314276 гена LIN28B ассоциирован с возрастом менархе у женщин Центрального Черноземья России. Акушерство и гинекология. 2019; 2: 98-104. [Ponomarenko I.V., Reshetnikov E.A., Polonikov A.V., Churnosov M.I. The polymorphic locus rs314276 of the gene LIN28B is associated with the age of menarche in women of the Central Black Soil Region of Russia. Akusherstvo I Ginekologiya/Obstetrics and Gynecology. 2019; 2: 98-104.(in Russian)]
  12. Пономаренко И.В., Полоников А.В., Чурносов М.И. Полиморфные локусы гена LHCGR ассоциированы с развитием лейомиомы матки. Акушерство и гинекология. 2018; 10: 86-91. [Ponomarenko I.V., Polonikov A.V., Churnosov M.I. The polymorphic loci of the LHCGR gene are associated with the development of uterine leiomyoma. Akusherstvo I Ginekologiya/Obstetrics and Gynecology. 2018; 10: 86-91. (in Russian)].
  13. Ong C.-T., Corces V.G. CTCF: An Architectural Protein Bridging Genome Topology and Function. Nature reviews Genetics. 2014;15(4):234-246. doi:10.1038/nrg3663.
  14. Tang Z., Luo O.J., Li X., Zheng M., Zhu J.J., Szalaj P., et al. CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription. Cell. 2015;163(7):1611–1627. doi.org/10.1016/j.cell.2015.11.024.
  15. Фархат К.Н., Савилова А.М., Макиян З.Н., Адамян Л.В. Эндометриоз: роль стволовых клеток в развитии заболевания (обзор литературы). Проблемы репродукции. 2016; 22(1): 20-27. [Farhat K.N., Savilova A.M., Makiyan Z.N., Adamyan L.V. Endometriosis: the role of stem cells in the development of the disease (literature review). Reproduction problems. 2016; 22 (1): 20-27. (in Russian)].
  16. Baranov V.S., Ivaschenko T.E., Yarmolinskaya M.I. Comparative system genetics view of endometriosis and uterine leiomyoma: Two sides of the same coin? Systems Biology in Reproductive Medicine. 2016;62(2):93-105.
  17. The GTEx Consortium. Genetic effects on gene expression across human tissues. Nature. 2017;550: 204–213.
  18. Stavrou I., Zois C., Chatzikyriakidou A., Georgiou I., Tsatsoulis A. Combined estrogen receptor α and estrogen receptor β genotypes influence the age of menarche. Hum. Reprod. 2006;21:554–557.
  19. Eren E., Koca B., Ture M., Guzel B. Epicardial Adiposity in Children with Obesity and Metabolic Syndrome. Iranian Journal of Pediatrics. 2014;24(4):411-417.
  20. Silva R.C., Costa I.R., Bordin B.M., Silva C.T., Souza S.R., Júnior C.L., et al. RsaI polymorphism of the ERβ gene in women with endometriosis. Genet Mol Res. 2011;10:465–470. doi: 10.4238/vol10-1gmr940.
  21. Zulli K., Bianco B., Mafra F.A., Teles J.S., Christofolini D.M., Barbosa C.P. Polymorphism of the estrogen receptor β gene is related to infertility and infertility-associated endometriosis. Arq Bras Endocrinol Metabol. 2010;54(6):567– 571.
  22. Шрамко С.В., Гуляева Л.Ф., Баженова Л.Г., Левченко В.Г. Миома матки и аденомиоз: молекулярная характеристика по экспрессии генов стероидных рецепторов. Акушерство и гинекология. 2018; 4: 58-63. [Shramko S.V., Gulyaeva L.F., Bazhenova L.G., Levchenko V.G. Uterine fibroids and adenomyosis: a molecular characterization of the expression of steroid receptor genes. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2018; 4: 58-63. (in Russian)]. https://dx.doi.org/10.18565/aig.2018.4.58-63
  23. Ducker G.S., Rabinowitz J.D. One-Carbon Metabolism in Health and Disease. Cell metabolism. 2017;25(1):27-42. doi:10.1016/j.cmet.2016.08.009.
  24. Sapkota Y., Steinthorsdottir V., Morris A.P., Fassbender A., Rahmioglu N., De Vivo I., et al. Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism. Nature Communications. 2017;8:15539. doi:10.1038/ncomms15539.
  25. Демакова Н.А. Молекулярно-генетические характеристики пациенток с гиперплазией и полипами эндометрия. Научный результат. Медицина и фармация. 2018; 4(2):26-39. [Demakova N.A. Molecular and genetic characteristics of patients with hyperplasia and endometric polyps. Research Result. Medicine and Pharmacy. 2018;4(2):26-39. (in Russian)]. DOI: 10.18413/2313-8955-2018-4-2-0-4
  26. Радзинский В.Е., Алтухова О.Б. Молекулярно-генетические детерминанты бесплодия при генитальном эндометриозе. Научные результаты биомедицинских исследований. 2018; 4(3):21-30. [Radzinsky V.E., Altuchova O.B. Molecular-genetic determinants of infertility in genital endometryosis. Research Results in Biomedicine. 2018;4(3):21-30. (in Russian)]. DOI: 10.18413/2313-8955-2018-4-3-0-3

Received 08.06.2018

Accepted 22.06.2018

About the Authors

Ponomarenko, Irina V., MD, associate professor, Department of Biomedical Disciplines of the Medical Institute, Belgorod State National Research University.
308015, Russia, Belgorod, Pobedy str. 85. Tel.: +74722301383. E-mail: ponomarenko_i@bsu.edu.ru. https://orcid.org/0000-0002-5652-0166.
Polonikov, Alexey V., MD, professor, head of the Department of Biology, Medical Genetics and Ecology, Kursk State Medical University,
Ministry of Health of Russia of the Ministry of Health of Russia. 305041, Russia, Kursk, K. Marx str. 3. Tel.: +74712588147. E-mail: polonikovav@kursksmu.net.
Churnosov, Mikhail I., MD, professor, head of the Department of Biomedical Disciplines Medical Faculty, Belgorod State National Research University.
308015, Russia, Belgorod, Pobedy str. 85. Tel.: +74722301383. E-mail: churnosov@bsu.edu.ru. http://orcid.org/0000-0003- 1254-6134

For citation: Ponomarenko I.V., Polonikov A.V., Churnosov M.I. Association of ESR2 rs4986938 polymorphism with the development of endometrial hyperplasia. Akusherstvo i Ginekologiya/Obstetrics and Gynecology.2019; (4): 66-72. (in Russian)
https://dx.doi.org/10.18565/aig.2019.4.66-72

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