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Estrogen receptor alpha XbaI-rs9340799 polymorphism involvement in Gender Dysphoria etiology
Abstracts
28 Estrogen receptor alpha XbaI-rs9340799 polymorphism involvement in Gender Dysphoria etiology R. Fernández Garcíaa, J. Cortés Cortésa, E. Gómez Gilb, I. Estevac, M.C. Almarazc, A. Guillamónd, E. Pásaroa
149
Conclusion: According to our data, and in conjunction with our previous work, both ERα and β are implicated in the etiology of GD. Our results suggest that genotype A/G favored cerebral feminization being a protective effect to the biological females and a risk effect for biological males. And a larger number of repeats in ERβ promotes a cerebral defeminization process.
a
UDC, A Coruña, Spain Hospital Clinic, Barcelona, Spain c Hospital Carlos Haya, Málaga, Spain d UNED, Madrid, Spain b
Gender dysphoria (GD), a marked incongruence between one’s experienced gender and biological sex, is commonly believed to arise from discrepant cerebral and genital sexual differentiation. Biological and environmental factors (deregulation of sex hormone levels during early fetal development) contribute to GD, but increasing evidence also supports the idea of genetic vulnerability. Our group previously found an association between estrogen receptor (ER) β and GD (Fernández et al., 2014a-b). Estrogens regulate many physiological processes by binding to their specific estrogen receptors, α or β, which belong to the family of ligandregulated transcription factors. Once bound by estrogens, the ER undergoes a conformational change allowing it to interact with high affinity with specific DNA sequences located in or near promoter regions of a wide set of target genes and modulating the transcription of multiple genes in a cascade process (Yang & Shah, 2014). Aim: To investigate the implication of polymorphism ERα-XbaI rs9340799 in GD. Methods: Analysis was performed in blood samples from 426 female-to-males (FtMs), 588 male-to-females (MtFs) and 1327 sex and ethnically-matched controls. The sample was recruited through the Andalucía Gender Identity Unit (Carlos Haya Hospital of Málaga, Spain) and the Gender Identity Unit of Cataluña (Clínic Hospital of Barcelona, Spain). All subjects were diagnosed with Transsexualism (F64.0) according to the ICD-10 or with Gender Identity Disorder in Adolescents or Adults (302.85) according to the DSM-IV-TR. The control groups consisted of two random groups of individuals diagnosed as not having GD, previously used in metabolic and genetic studies, who were pair-matched for chromosomal sex, ethnicity and geographical origin. The exclusion criteria were head trauma, neurological disorder, and history of alcohol and/or drug abuse. a.Molecular Analysis Genomic DNA was extracted from EDTA blood samples using the DNeasy Blood & Tissue Kit from Qiagen. The ERα-XbaI polymorphism was analyzed by PCR-RFLP as suggested by van Meurs (2003). Absence of restriction sites was specified as G, and the resulting genotypes were G/G, A/G, and A/A b.Statistical methods The analyses were performed using SPSS® 23.0 with a p b 0.05 as significant, and by the free online software SNPStats http:// bioinfo.iconcologia.net/SNPstats Results: The genotype frequencies were in Hardy-Weinberg equilibrium. The allele and genotype frequencies for the ERα-XbaI polymorphism were significantly different between FtM and XX control group (χ2 = 4.049; p = 0.044 and χ2 = 11.237; p = 0.004) but not significantly different between the MtF and XY control group (χ2=2.686; p= 0.101 and χ2 =5.366; p =0.068). The interaction analysis with the chromosomal sex covariate showed that genotype A/G has a protective effect for biological females [OR= 0.38 (0.210.67); p =0.00031] while the same genotype has a high risk effect for biological males [OR=1.92 (1.10-3.34)); p=0.00031].
doi:10.1016/j.jpsychores.2017.03.238
29 INTERMED-Self Assessment (IMSA): Validity and preliminary applications in research S. Ferraria, A.K. Van Reedt Dortlandb, A. Boeninkb a
University of Modena & Reggio Emilia, Modena, Italy VU University Medical Centre/GGZ in Geest, Amsterdam, Netherlands
b
Aims: The INTERMED Self-Assessment questionnaire (IM-SA) was developed as an alternative to the INTERMED Complexity Assessment Grid interview (IM-CAG) to assess biopsychosocial complexity and health care needs in order to optimize care. The aim of this study was to discuss possible applications of IMSA to routine clinical work in a CL psychiatry setting, after presenting IM-SA’s feasibility, reliability, validity and predictive value for health care utilization (HCU) and quality of life (QoL) as emerged by the IMSA Study. Methods: The IMSA Study was an international multicentric prospective observational cohort study, involving 850 participants who completed both the IM-SA and IM-CAG. Feasibility by percentages of missing values, reliability by Cronbach’s alpha, inter-rater agreement by intraclass correlation coefficients (ICCs) and convergent validity of IM-SA scores with mental health (SF-36 mental health subscale and HADS) and medical health (CIRS) and discriminant validity of IM-SA scores with QoL (EQ-5D) by Spearmans rank correlations were determined. Predictive validity of IM-SA scores with HCU and QoL were examined by (generalized) linear mixed models. At Modena University Hospital, IMSA was included in several clinical research protocols to support screening procedures. Results: Feasibility, face validity and reliability (Cronbach’s alpha 0.80) were satisfactory. ICC between IM-SA and IM-CAG total scores were .78 (95% CI .75–.81). Correlations of the IM-SA with the SF-36, HADS, CIRS and EQ-5D were -.65, .002, .28 and -.59 respectively. The IM-SA predicted HCU and QoL after 3and 6-month follow-up. Seven subjects suffering from comorbid HIV and depression and 30 subjects undergoing colonoscopy for screening were also tested with IM-SA. Mean baseline score was 17.14 (SD = 8.71) for the depressed HIV subjects, with 2 subjects overcoming the cutoff of 21, suggesting clinical complexity. Mean score was 7.72 (SD = 4.19) for subjects undergoing colonoscopy, none of whom reached a score suggesting clinical complexity. Conclusion: The IM-SA may efficiently support healthcare professionals in the assessment of patient’s biopsychosocial complexity aimed at providing integrated, personalized multidisciplinary care. Inclusion of IMSA as a routine screening tool may be advised in different clinical inand out-patient contexts.
doi:10.1016/j.jpsychores.2017.03.239
28 Estrogen receptor alpha XbaI-rs9340799 polymorphism involvement in Gender Dysphoria etiology R. Fernández Garcíaa, J. Cortés Cortésa, E. Gómez Gilb, I. Estevac, M.C. Almarazc, A. Guillamónd, E. Pásaroa
149
Conclusion: According to our data, and in conjunction with our previous work, both ERα and β are implicated in the etiology of GD. Our results suggest that genotype A/G favored cerebral feminization being a protective effect to the biological females and a risk effect for biological males. And a larger number of repeats in ERβ promotes a cerebral defeminization process.
a
UDC, A Coruña, Spain Hospital Clinic, Barcelona, Spain c Hospital Carlos Haya, Málaga, Spain d UNED, Madrid, Spain b
Gender dysphoria (GD), a marked incongruence between one’s experienced gender and biological sex, is commonly believed to arise from discrepant cerebral and genital sexual differentiation. Biological and environmental factors (deregulation of sex hormone levels during early fetal development) contribute to GD, but increasing evidence also supports the idea of genetic vulnerability. Our group previously found an association between estrogen receptor (ER) β and GD (Fernández et al., 2014a-b). Estrogens regulate many physiological processes by binding to their specific estrogen receptors, α or β, which belong to the family of ligandregulated transcription factors. Once bound by estrogens, the ER undergoes a conformational change allowing it to interact with high affinity with specific DNA sequences located in or near promoter regions of a wide set of target genes and modulating the transcription of multiple genes in a cascade process (Yang & Shah, 2014). Aim: To investigate the implication of polymorphism ERα-XbaI rs9340799 in GD. Methods: Analysis was performed in blood samples from 426 female-to-males (FtMs), 588 male-to-females (MtFs) and 1327 sex and ethnically-matched controls. The sample was recruited through the Andalucía Gender Identity Unit (Carlos Haya Hospital of Málaga, Spain) and the Gender Identity Unit of Cataluña (Clínic Hospital of Barcelona, Spain). All subjects were diagnosed with Transsexualism (F64.0) according to the ICD-10 or with Gender Identity Disorder in Adolescents or Adults (302.85) according to the DSM-IV-TR. The control groups consisted of two random groups of individuals diagnosed as not having GD, previously used in metabolic and genetic studies, who were pair-matched for chromosomal sex, ethnicity and geographical origin. The exclusion criteria were head trauma, neurological disorder, and history of alcohol and/or drug abuse. a.Molecular Analysis Genomic DNA was extracted from EDTA blood samples using the DNeasy Blood & Tissue Kit from Qiagen. The ERα-XbaI polymorphism was analyzed by PCR-RFLP as suggested by van Meurs (2003). Absence of restriction sites was specified as G, and the resulting genotypes were G/G, A/G, and A/A b.Statistical methods The analyses were performed using SPSS® 23.0 with a p b 0.05 as significant, and by the free online software SNPStats http:// bioinfo.iconcologia.net/SNPstats Results: The genotype frequencies were in Hardy-Weinberg equilibrium. The allele and genotype frequencies for the ERα-XbaI polymorphism were significantly different between FtM and XX control group (χ2 = 4.049; p = 0.044 and χ2 = 11.237; p = 0.004) but not significantly different between the MtF and XY control group (χ2=2.686; p= 0.101 and χ2 =5.366; p =0.068). The interaction analysis with the chromosomal sex covariate showed that genotype A/G has a protective effect for biological females [OR= 0.38 (0.210.67); p =0.00031] while the same genotype has a high risk effect for biological males [OR=1.92 (1.10-3.34)); p=0.00031].
doi:10.1016/j.jpsychores.2017.03.238
29 INTERMED-Self Assessment (IMSA): Validity and preliminary applications in research S. Ferraria, A.K. Van Reedt Dortlandb, A. Boeninkb a
University of Modena & Reggio Emilia, Modena, Italy VU University Medical Centre/GGZ in Geest, Amsterdam, Netherlands
b
Aims: The INTERMED Self-Assessment questionnaire (IM-SA) was developed as an alternative to the INTERMED Complexity Assessment Grid interview (IM-CAG) to assess biopsychosocial complexity and health care needs in order to optimize care. The aim of this study was to discuss possible applications of IMSA to routine clinical work in a CL psychiatry setting, after presenting IM-SA’s feasibility, reliability, validity and predictive value for health care utilization (HCU) and quality of life (QoL) as emerged by the IMSA Study. Methods: The IMSA Study was an international multicentric prospective observational cohort study, involving 850 participants who completed both the IM-SA and IM-CAG. Feasibility by percentages of missing values, reliability by Cronbach’s alpha, inter-rater agreement by intraclass correlation coefficients (ICCs) and convergent validity of IM-SA scores with mental health (SF-36 mental health subscale and HADS) and medical health (CIRS) and discriminant validity of IM-SA scores with QoL (EQ-5D) by Spearmans rank correlations were determined. Predictive validity of IM-SA scores with HCU and QoL were examined by (generalized) linear mixed models. At Modena University Hospital, IMSA was included in several clinical research protocols to support screening procedures. Results: Feasibility, face validity and reliability (Cronbach’s alpha 0.80) were satisfactory. ICC between IM-SA and IM-CAG total scores were .78 (95% CI .75–.81). Correlations of the IM-SA with the SF-36, HADS, CIRS and EQ-5D were -.65, .002, .28 and -.59 respectively. The IM-SA predicted HCU and QoL after 3and 6-month follow-up. Seven subjects suffering from comorbid HIV and depression and 30 subjects undergoing colonoscopy for screening were also tested with IM-SA. Mean baseline score was 17.14 (SD = 8.71) for the depressed HIV subjects, with 2 subjects overcoming the cutoff of 21, suggesting clinical complexity. Mean score was 7.72 (SD = 4.19) for subjects undergoing colonoscopy, none of whom reached a score suggesting clinical complexity. Conclusion: The IM-SA may efficiently support healthcare professionals in the assessment of patient’s biopsychosocial complexity aimed at providing integrated, personalized multidisciplinary care. Inclusion of IMSA as a routine screening tool may be advised in different clinical inand out-patient contexts.
doi:10.1016/j.jpsychores.2017.03.239