The Role of Genetic Factors in Gender Dysphoria

Öz

The dissatisfaction of individuals with their existing biological sex and feeling of belonging to the opposite sex is defined as gender dysphoria. Many environmental factors and genetic features are effective in the emergence of this behavior. Studies investigating the genetic basis of this condition, which leads to serious changes in people's lives, are relatively new. In this review, the studies investigating the genetic basis of this behavioral pattern in individuals with gender dysphoria are examined and information that will guide for future researches is presented.

Anahtar Kelimeler

• Cytogenetic studies,epigenetic studies,gender dysphoria,molecular genetic studies

Cinsiyet Disforisinde Genetik Faktörlerin Rolü

Öz

Bireylerin mevcut biyolojik cinsiyetlerinden hoşnutsuzlukları ve karşıt cinsiyete ait hissetme durumu cinsiyet disforisi olarak tanımlanır. Bu davranış özelliğinin oluşmasında çevresel birçok faktörün yanı sıra kişilerin kendine has genetik özellikleri de etkilidir. Kişilerin yaşamında köklü değişikliklere neden olan bu durumun genetik temelini araştıran çalışmalar nispeten yenidir. Bu derlemede, cinsiyet disforisi olan bireylerde bu davranış paterninin genetik temelini araştıran çalışmalar irdelenmiş ve gelecek araştırmalar için yol gösterici olacak bilgilere yer verilmiştir.

Anahtar Kelimeler

• Cinsiyet disforisi,epigenetik çalışmalar,moleküler genetik çalışmalar,sitogenetik çalışmalar

Kaynakça

1. 1. Rey R, Josso N, Racine C. Sexual Differentiation. 2016 [cited 08.08.2019]. In: Endotext [Internet] [Internet]. South Dartmouth (MA): MDText.com, Inc., [cited 08.08.2019]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279001/.
2. 2. Arnold AP. A general theory of sexual differentiation. Journal of neuroscience research. 2017 Jan 2;95(1-2):291-300
3. 3. Fisher AD, Ristori J, Morelli G, Maggi M. The molecular mechanisms of sexual orientation and gender identity. Molecular and cellular endocrinology. 2018 May 15;467:3-13
4. 4. Zucker KJ, Lawrence AA, Kreukels BP. Gender Dysphoria in Adults. Annual review of clinical psychology. 2016;12:217-247
5. 5. McCarthy MM, Arnold AP. Reframing sexual differentiation of the brain. Nature neuroscience. 2011 Jun;14(6):677-683
6. 6. Association AP. Gender Dysphoria. Diagnostic and Statistical Manual of Mental Disorders (DSM-5). 5th ed. Washington, DC and London: American Psychiatric Publishing; 2013. p. 451-460.
7. 7. Organization WH. ICD-11 for Mortality and Morbidity Statistics (04/2019 Version) [cited 2019 09.08.2019]. Available from: https://icd.who.int/browse11/l‐m/en.
8. 8. Arcelus J, Bouman WP, Van Den Noortgate W, Claes L, Witcomb G, Fernandez-Aranda F. Systematic review and meta-analysis of prevalence studies in transsexualism. European psychiatry : the journal of the Association of European Psychiatrists. 2015 Sep;30(6):807-815

9. 9. Sasaki S, Ozaki K, Yamagata S, Takahashi Y, Shikishima C, Kornacki T, et al. Genetic and Environmental Influences on Traits of Gender Identity Disorder: A Study of Japanese Twins Across Developmental Stages. Archives of sexual behavior. 2016 Oct;45(7):1681-1695
10. 10. Polderman TJC, Kreukels BPC, Irwig MS, Beach L, Chan YM, Derks EM, et al. The Biological Contributions to Gender Identity and Gender Diversity: Bringing Data to the Table. Behavior genetics. 2018 Mar;48(2):95-108
11. 11. Hengstschlager M, van Trotsenburg M, Repa C, Marton E, Huber JC, Bernaschek G. Sex chromosome aberrations and transsexualism. Fertility and sterility. 2003 Mar;79(3):639-640
12. 12. Bearman G. Karyotyping and genetics in the transgendered population. In: Ettner R, Monstrey S, Eyler AE, editors. Principles of transgender medicine and surgery. Binghamton: The Haworth Press; 2007. p. 223–232.
13. 13. Wylie KR, Steward D. A consecutive series of 52 transsexual people presenting for assessment and chromosomal analysis at a gender identity clinic. Int J Transgenderism 2008;10:147-148
14. 14. Vujovic S, Popovic S, Sbutega-Milosevic G, Djordjevic M, Gooren L. Transsexualism in Serbia: a twenty-year follow-up study. The journal of sexual medicine. 2009 Apr;6(4):1018-1023
15. 15. Inoubli A, De Cuypere G, Rubens R, Heylens G, Elaut E, Van Caenegem E, et al. Karyotyping, is it worthwhile in transsexualism? The journal of sexual medicine. 2011 Feb;8(2):475-478
16. 16. Auer MK, Fuss J, Stalla GK, Athanasoulia AP. Twenty years of endocrinologic treatment in transsexualism: analyzing the role of chromosomal analysis and hormonal profiling in the diagnostic work-up. Fertility and sterility. 2013 Oct;100(4):1103-1110
17. 17. Fernandez R, Guillamon A, Gomez-Gil E, Esteva I, Almaraz MC, Cortes-Cortes J, et al. Analyses of karyotype by G-banding and high-resolution microarrays in a gender dysphoria population. Genes & genomics. 2018 May;40(5):465-473
18. 18. Koolen DA, Kramer JM, Neveling K, Nillesen WM, Moore-Barton HL, Elmslie FV, et al. Mutations in the chromatin modifier gene KANSL1 cause the 17q21.31 microdeletion syndrome. Nature genetics. 2012 Apr 29;44(6):639-641
19. 19. Natacci F, Alfei E, Tarara L, D'Arrigo S, Zuffardi O, Gentilin B, et al. Chromosome 17q21.31 duplication syndrome: Description of a new familiar case and further delineation of the clinical spectrum. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2016 Jan;20(1):183-187
20. 20. Yang F, Zhu XH, Zhang Q, Sun NX, Ji YX, Ma JZ, et al. Genomic Characteristics of Gender Dysphoria Patients and Identification of Rare Mutations in RYR3 Gene. Scientific reports. 2017 Aug 21;7(1):8339
21. 21. Bentz EK, Hefler LA, Kaufmann U, Huber JC, Kolbus A, Tempfer CB. A polymorphism of the CYP17 gene related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism. Fertility and sterility. 2008 Jul;90(1):56-59
22. 22. Fernandez R, Cortes-Cortes J, Esteva I, Gomez-Gil E, Almaraz MC, Lema E, et al. The CYP17 MspA1 Polymorphism and the Gender Dysphoria. The journal of sexual medicine. 2015 Jun;12(6):1329-1333
23. 23. Fernández R, Cortés-Cortés J, Gómez-Gil E, Esteva I, Almaraz MC, Guillamón A, et al. The CYP17-MspA1 rs743572 polymorphism is not associated with gender dysphoria. Genes & genomics. 2016;38:1145-1150
24. 24. Lombardo F, Toselli L, Grassetti D, Paoli D, Masciandaro P, Valentini F, et al. Hormone and genetic study in male to female transsexual patients. Journal of endocrinological investigation. 2013 Sep;36(8):550-557
25. 25. 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 Aug;30(7):657-664
26. 26. Hare L, Bernard P, Sanchez FJ, Baird PN, Vilain E, Kennedy T, et al. Androgen receptor repeat length polymorphism associated with male-to-female transsexualism. Biological psychiatry. 2009 Jan 1;65(1):93-96
27. 27. Fernandez R, Esteva I, Gomez-Gil E, Rumbo T, Almaraz MC, Roda E, et al. Association study of ERbeta, AR, and CYP19A1 genes and MtF transsexualism. The journal of sexual medicine. 2014 Dec;11(12):2986-2994
28. 28. Fernandez R, Esteva I, Gomez-Gil E, Rumbo T, Almaraz MC, Roda E, et al. The (CA)n polymorphism of ERbeta gene is associated with FtM transsexualism. The journal of sexual medicine. 2014 Mar;11(3):720-728
29. 29. Ujike H, Otani K, Nakatsuka M, Ishii K, Sasaki A, Oishi T, et al. Association study of gender identity disorder and sex hormone-related genes. Progress in neuro-psychopharmacology & biological psychiatry. 2009 Oct 1;33(7):1241-1244
30. 30. Cortes-Cortes J, Fernandez R, Teijeiro N, Gomez-Gil E, Esteva I, Almaraz MC, et al. Genotypes and Haplotypes of the Estrogen Receptor alpha Gene (ESR1) Are Associated With Female-to-Male Gender Dysphoria. The journal of sexual medicine. 2017 Mar;14(3):464-472