Skeleton formation and polymorphism of androgen receptor gene in transsexual individuals


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Abstract

Introduction. The androgen receptor (AR) gene MIGHR is known to be associated with transsexualism. Bone tissue is one of the target organs for androgens. Trochanteric index (TI) (ratio of height to the leg length) may indicate the organism androgenization level during puberty. It is interesting to identify the peculiarities of this process in the trans-person population. The aim of the study. To identify the connection between androgen receptor (AR) gene CAG-polymorphism and skeletal formation type in transgender persons.Methods. The study involved 262 patients above 18 years with the diagnosis of transsexualism (121 MtF, 141 FtM). Mental and sexual status; trochanteric index (TI); and genetic analysis (AR gene polymorphism) was estimated. Results. The average TI in the MtF group accounts for 1,93±0,03, which represents hypo-evolutive type of skeletal development. For FtM group TI was 2,01±0,04, that matches frontier between normal evolutive and hyper-evolutionary types. Differences in TI values in the MtF and FtM were significant (p=0,000). The MtF and FtM groups showed significant differences in the number of СAG repeats (p=0,000). A strong negative correlation was found between the TI value and number of CAG repeats in both groups (R=-0,24; p=0,000). Conclusion. TI is associated with polymorphism of AR. FtM population is characterized by a less number of CAG repeats in the AR gene compared to MtF, a higher TI, and a tendency toward a hyper-evolutionary type of the formation of the skeleton. The MtF population otherwise is characterized by a hypo-evolutive type of the formation of the skeleton.

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About the authors

N. V Solov’eva

Scientific Center of Personalized Medicine

Email: vilianov1@mail.ru
Bolshaya Pochtovaya str., 20/3, Moscow, 105082, Russian Federation

E. V Makarova

Scientific Center of Personalized Medicine; National Medical Research Center for Rehabilitation and Balneology

Email: vilianov1@mail.ru
Bolshaya Pochtovaya str., 20/3, Moscow, 105082, Russian Federation; Novyi Arbat, 32, Moscow, 121099, Russian Federation

V. B Vil’yanov

Scientific Center of Personalized Medicine

Email: vilianov1@mail.ru
Bolshaya Pochtovaya str., 20/3, Moscow, 105082, Russian Federation

S. A Kremenitskaya

Scientific Center of Personalized Medicine

Email: vilianov1@mail.ru
Bolshaya Pochtovaya str., 20/3, Moscow, 105082, Russian Federation

S. V Chausova

N.I. Pirogov Russian National Research Medical University

Email: vilianov1@mail.ru
Ostrovityanova str. 1, Moscow, 117997, Russian Federation

I. V Kichuk

N.I. Pirogov Russian National Research Medical University

Email: vilianov1@mail.ru
Ostrovityanova str. 1, Moscow, 117997, Russian Federation

D. V Shibalev

Institute of Gene Biology

Email: vilianov1@mail.ru
Vavilova str. 34/5, Moscow, 119334, Russian Federation

V. A Vasilyev

Institute of Gene Biology

Email: vilianov1@mail.ru
Vavilova str. 34/5, Moscow, 119334, Russian Federation

References

  1. Arnold A.P. Mouse models for avaluating sex chromosome effects that causesex differences in non-gonadal tissues. J. of Neuroendocrinology. 2009; 21: 377-86.
  2. Arnold A.P The organizational-activational hypothesis as the foundation for a unified theory of sexual differentiation of oll mammalian tissues. Hormones and Behavior. 2009; 55: 570-8.
  3. Kreukels B.PC., Steensma T.D., de Vries A.L.C. Gender Dysphoria and Disorders of Sex Development. Progress in Care and Knowledge. Focus on Sexuality Research. Sprinter US: Sprinter Science+Business Media New York, 2014; 357.
  4. Lin L.H., Baracat M.C.P., Maciel G.A.R., Soares J.M.J, Baracat E.C. Androgen receptor gene polymorphism and polycystic ovary syndrome. International J. of Gynaecology and Obstetrics. 2012; 120: 115-8.
  5. Rosa Fernandez, Isabel Esteva, Esther Gomez-Gil, Teresa Rumbo, Mari Cruz Almaraz, Ester Roda, Juan-Jesus Haro-Mora, Antonio Guillamon, Eduardo Pasaro, Association Study of ERp, AR, and CYP19A1 Genes and MtF Transsexualism. J. Sex Med. 2014; 11: 2986-94.
  6. Stevens J.R. Schizophrenia: Reproductive Hormones and the Brain. Am. J. Psychiatry. 2002; 159: 713-9.
  7. Crocoll A., Zhu C.C., Cato A.C., Blum M. Expression of androgen receptor mRNA during mouse embryogene_sis. Mech. Dev. 1998; 72 (1/2): 175-8.
  8. Фесай О.А., Кравченко С.А., Тыркус М.Я., Макух Г.В., Зинченко В.М., Стрелко Г.В., Лившиц Л.А. CAG- полиморфизм гена андроенового рецептора у мужчин с азооспермией и олигоспермией из Украины. Цитология и генетика. 2009; 6: 45-51. [Fesaj O.A., Kravchenko S.A., Tyrkus M.YA., Makuh G.V, Zinchenko V.M., Strelko G.V, Livshic L.A. CAG- polimorfizm gena androe-novogo receptora u muzhchin s azoosper-miej i oligospermiej iz Ukrainy Citologiya i genetika. 2009; 6: 45-51 (in Russian)]
  9. Chamberlain N.L., Driver E.D., Miesfeld R.L. The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function. Nucleic Acids Research. 1994; 22 (15): 3181-6.
  10. Kenny A.M., McGee D., Joseph C. et al. Lack of association between androgen receptor polymorphisms and bone mineral density or physical function in older men. Endocrine research. 2005; 31 (4): 285-93.
  11. Zitzmann M., Brune M., Kornmann B. et al. The CAG repeat polymorphism in the androgen receptor gene affects bone density and bone metabolism in healthy males. Clinical endocrinology 2001; 55 (5): 649-57.
  12. Hare L., Bernard P, Sanchez F.J., Baird P.N., Vilain E., Kennedy T., et al. (2009). Androgen receptor repeat length polymorphism associated with male-to-female transsexualism. Biological Psychiatry. 2009; 65: 93-6.
  13. Henningsson S., Westberg L., Nilsson S., Lundstrom B., Ekselius L., Bodlund O. et al. Sex steroid-related genes and male-to-female transsexualism. Psychoneuroendocrinology 2005; 30: 657-64.
  14. Rosa Fernandez, Isabel Esteva, Esther Gomez-Gil, Teresa Rumbo, Mari Cruz Almaraz, Ester Roda, Juan-Jesus Haro-Mora, Antonio Guillamon and Eduardo Pasaro. The (CA)n Polymorphism of ERp Gene is Associated with FtM Transsexualism. J. Sex. Med. 2014; 11: 720-8.
  15. Nur-Vaizura Mohamad, Ima-Nirwana Soe-laiman, Kok-Yong Chin. A concise review of testosterone and bone health. Clin. Interv Aging. 2016; 11: 1317-24. Published online 2016 Sep 22. https://doi.org/10.2147/CIA. S115472PMCID: PMC5036835
  16. Androgens and BoneBart L. Clarke, Sundeep KhoslaSteroids. Author manuscript; available in PMC 2010 Mar 1. Published in final edited form as: Steroids. 2009; 74 (3): 296-305. Published online 2008 Oct 17. https://doi.org/10.10Wj. steroids.2008.10.003PMCID: PMC2679948
  17. Feng X., McDonald J.M. Disorders of bone remodeling. Annu Rev Pathol. 2011; 6: 121-45.
  18. Hadjidakis D.J., Androulakis I.I. Bone remodeling. Ann N Y Acad Sci. 2006; 1092 (1): 385-96.
  19. Phillip M., Maor G., Assa S., Silbergeld A., Segev Y. Testosterone stimulates growth of tibial epiphyseal growth plate and insulinlike growth factor-1 receptor abundance in hypophysectomized and castrated rats. Endocrine. 2001; 16 (1): 1-6.
  20. Васильченко Г.С. Сексопатология. Г.С. Васильченко, С.Г Агаркова, С.Г Агарков и др.: справочник. М.: Медицина, 1990; 576
  21. Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7. World Professional Association for Transgender Health, 2011.
  22. Морозова Е.В., Прилепа С.А.Генетические аспекты становления половой самоидентификации и возникновение гендерной дисфории. Вестник новых медицинских технологий. 2017; 1: 203-18.
  23. Rachel A. Davey, Mathis Grossmann. Androgen Receptor Structure, Function and Biology: From Bench to Bedside. Clin Biochem Rev. 2016; 37 (1): 3-15. PMCID: PMC4810760 PMID: 27057074
  24. Торшин И.Ю., Громова О.А., Сухих Г.Т., Галицкая С.А, Юргель И.С Молекулярные механизмы дидрогестерона (Дюфастон®). Полногеномное исследование транскрипционных эффектов рецепторов прогестерона, андрогенов и эстрогенов. Гинекология. 2009; 11 (5): 9-15.

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