Analysis of Four Polymorphisms Located at the Promoter of the Estrogen Receptor Alpha ESR1 Gene in a Population With Gender Incongruence

[Abstract] Introduction: Gender incongruence defines a state in which individuals feel discrepancy between the sex assigned at birth and their gender. Some of these people make a social transition from male to female (transwomen) or from female to male (trans men). By contrast, the word cisgender describes a person whose gender identity is consistent with their sex assigned at birth. Aim: To analyze the implication of the estrogen receptor a gene (ESR1) in the genetic basis of gender incongruence. Main Outcome Measures: Polymorphisms rs9478245, rs3138774, rs2234693, rs9340799. Method: We carried out the analysis of 4 polymorphisms located at the promoter of the ESR1 gene (C1 ¼ rs9478245, C2 ¼ rs3138774, C3 ¼ rs2234693, and C4 ¼ rs9340799) in a population of 273 trans women, 226 trans men, and 537 cis gender controls. For SNP polymorphisms, the allele and genotype frequencies were analyzed by c2 test. The strength of the SNP associations with gender incongruence was measured by binary logistic regression. For the STR polymorphism, the mean number of repeats were analyzed by the ManneWhitney U test. Measurement of linkage disequilibrium and haplotype frequencies were also performed. Results: The C2 median repeats were shorter in the trans men population. Genotypes S/S and S/L for the C2 polymorphism were overrepresented in the trans men group (P ¼ .012 and P ¼ .003 respectively). We also found overtransmission of the A/A genotype (C4) in the trans men population (P ¼ .017), while the A/G genotype (C4) was subrepresented (P ¼ .009]. The analyzed polymorphisms were in linkage disequilibrium. In the trans men population, the T(C1)-L(C2)-C(C3)-A(C4) haplotype was overrepresented (P ¼ .019) while the T(C1)-L(C2)-C(C3)-G(C4) was subrepresented (P ¼ .005). Conclusion: The ESR1 is associated with gender incongruence in the trans men populationThis work was supported by grants: ED431B 019/02 (EP), PGC2018-094919-B-C21 (AG), PGC2018-094919-B-C22 (RF), and FPU 15/02558 (JCC)Xunta de Galicia; ED431B 019/0

Implications of the Estrogen Receptor Coactivators SRC1 and SRC2 in the Biological Basis of Gender Incongruence

[Abstract] Introduction Brain sexual differentiation results from the effects of sex steroids on the developing brain. The presumptive route for brain masculinization is the direct induction of gene expression via activation of the estrogen receptors α and β and the androgen receptor through their binding to ligands and to coactivators, regulating the transcription of multiple genes in a cascade effect. Aim To analyze the implication of the estrogen receptor coactivators SRC-1, SRC-2, and SRC-3 in the genetic basis of gender incongruence. Main Outcome Measures Analysis of 157 polymorphisms located at the estrogen receptor coactivators SRC-1, SRC-2, and SRC-3, in 94 transgender versus 94 cisgender individuals. Method Using SNPStats software, the allele and genotype frequencies were analyzed by χ2, the strength of the association was measured by binary logistic regression, estimating the odds ratio for each genotype. Measurements of linkage disequilibrium and haplotype frequencies were also performed. Results We found significant differences at level P < .05 in 8 polymorphisms that correspond to 5.09% of the total. Three were located in SRC-1 and 5 in SRC-2. The odds ratio analysis showed significant differences at level P < .05 for multiple patterns of inheritance. The polymorphisms analyzed were in linkage disequilibrium. The SRC-1 haplotypes CGA and CGG (global haplotype association P < .009) and the SRC-2 haplotypes GGTAA and GGTAG (global haplotype association P < .005) were overrepresented in the transgender population. Conclusion The coactivators SRC-1 and SRC-2 could be considered as candidates for increasing the list of potential genes for gender incongruence. Ramírez KDV, Fernández R, Delgado-Zayas E, et al. Implications of the Estrogen Receptor Coactivators SRC1 and SRC2 in the Biological Basis of Gender Incongruence. Sex Med 2021;9:100368.This work was supported by grants: ED431B 019/02 (EP), PGC2018-094919-B-C21 (AG), PGC2018-094919-B-C22 (RF and EP

Consumption of cows' milk is associated with lower risk of type 2 diabetes mellitus. A cross-sectional study

The aim of this prospective, adult population-based study was to analyse the prevalence of type 2 diabetes mellitus in relation to the intake of cows' milk and the prevalence of anti-beta-lactoglobulin (anti-β-LG) antibodies. Measurements were made of weight, height, levels of anti-islet antibodies, anti-β-LG antibodies and tumour necrosis factor alpha (TNF-α) in all the participants. The likelihood of having positive anti-β-LG antibodies was higher in subjects who consumed milk more frequently. Subjects who consumed milk less than once per day were more likely to have type 2 diabetes than those who consumed milk more than once per day. The levels of TNF-α were significantly higher in individuals with positive anti-β-LG antibodies and in those who consumed milk more often. The prevalence of anti-β-LG antibodies was associated with the intake of milk and with the TNF-α levels, but not with the prevalence of type 2 diabetes. © 2012 Elsevier Ltd.This study was supported by the CIBER in Diabetes and Associated Metabolic Disorders (Instituto de Salud Carlos III); Ministerio de Ciencia e Innovación (JCI-2010-08372) and Consejería Innovación, Ciencia y Empresa (P09-CTS-5125)

Gender-Affirming Hormone Therapy Modifies the CpG Methylation Pattern of the ESR1 Gene Promoter After Six Months of Treatment in Transmen

[Abstract] Background Brain sexual differentiation is a process that results from the effects of sex steroids on the developing brain. Evidence shows that epigenetics plays a main role in the formation of enduring brain sex differences and that the estrogen receptor α (ESR1) is one of the implicated genes. Aim To analyze whether the methylation of region III (RIII) of the ESR1 promoter is involved in the biological basis of gender dysphoria. Methods We carried out a prospective study of the CpG methylation profile of RIII (−1,188 to −790 bp) of the ESR1 promoter using bisulfite genomic sequencing in a cisgender population (10 men and 10 women) and in a transgender population (10 trans men and 10 trans women), before and after 6 months of gender-affirming hormone treatment. Cisgender and transgender populations were matched by geographical origin, age, and sex. DNAs were treated with bisulfite, amplified, cloned, and sequenced. At least 10 clones per individual from independent polymerase chain reactions were sequenced. The analysis of 671 bisulfite sequences was carried out with the QUMA (QUantification tool for Methylation Analysis) program. Outcomes The main outcome of this study was RIII analysis using bisulfite genomic sequencing. Results We found sex differences in RIII methylation profiles in cisgender and transgender populations. Cismen showed a higher methylation degree than ciswomen at CpG sites 297, 306, 509, and at the total fragment (P ≤ .003, P ≤ .026, P ≤ .001, P ≤ .006). Transmen showed a lower methylation level than trans women at sites 306, 372, and at the total fragment (P ≤ .0001, P ≤ .018, P ≤ .0107). Before the hormone treatment, transmen showed the lowest methylation level with respect to cisgender and transgender populations, whereas transwomen reached an intermediate methylation level between both the cisgender groups. After the hormone treatment, transmen showed a statistically significant methylation increase, whereas transwomen showed a non-significant methylation decrease. After the hormone treatment, the RIII methylation differences between transmen and transwomen disappeared, and both transgender groups reached an intermediate methylation level between both the cisgender groups. Clinical Implications Clinical implications in the hormonal treatment of trans people. Strengths & Limitations Increasing the number of regions analyzed in the ESR1 promoter and increasing the number of tissues analyzed would provide a better understanding of the variation in the methylation pattern. Conclusions Our data showed sex differences in RIII methylation patterns in cisgender and transgender populations before the hormone treatment. Furthermore, before the hormone treatment, transwomen and transmen showed a characteristic methylation profile, different from both the cisgender groups. But the hormonal treatment modified RIII methylation in trans populations, which are now more similar to their gender. Therefore, our results suggest that the methylation of RIII could be involved in gender dysphoria.This work was supported by grants: Xunta de Galicia ED431 B 019/02 (EP), PGC2018-094919-B-C21 (AG), Ministerio de ciencia, innovación y Universidades PGC2018-094919-B-C22 (RF, EP). J. Cortés-Cortés was supported by a doctoral fellowship FPU 15/02558Xunta de Galicia ED431 B 019/0

Telemedicine, Psychology and Diabetes: Evaluation of results and cost analysis

The Psychosocial Aspects of Diabetes (PSAD) Study Group is an official Study Group of the European Association for the Study of Diabetes (EASD).AIMS: Evidences of benefits of telemedicine in T1DM patients on continuous subcutaneous insulin infusion (CSII) treatment are limited. Aims: 1) to analyse the differences in clinical and psychological variables between subjects with T1DM on CSII treatment who were included in a Telecare (TC) program, and subjects with T1DM on CSII treatment who received Conventional care (CC); 2) Perform a cost analysis of the use of telemedicine in DM1 patients treated with CSII (TC versus CC). METHODS and PARTICIPANTS: Cross-over randomized clinical trial with duration of 18 months. 51 patients signed informed consent. Participants were randomly assigned to receive TC program or CC during 6 months, and after a 3 months wash-out period, patients changed to CC or to TC respectively. TC program included monthly visits using an Internet platform. CC comprised face-to-face visits every three months. Sociodemographic, clinical and psychological data was measured at the beginning and at the end of TC and CC. The direct and indirect costs were also measured. T Student was performed to assess differences between first and last visits in both groups (TC / CC). RESULTS: Patients with telemedicine at the end of treatment, have fewer hyperglycemia / week, less distress and greater adherence. Considering both direct and indirect costs, the cost per treatment (TC / CC) is similar. CONCLUSIONS: Telemedicine has significant implications for clinical and psychological variables and has the same cost (total) than the conventional treatment. Therefore, it can be a useful alternative for treatment of DM1 patients with CSII. However, studies with a larger sample size are needed.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Treatment profile of acute media otitis in a primary health centre

Objectiu: Descriure el tractament emprat a la otitis mitjana aguda (OMA) en adults i l’adherència als protocols i guies clíniques actuals. Disseny: Estudi descriptiu transversal i retrospectiu. Àmbit: Centre de Salut Sa Torre de Manacor de l’Àrea de Salut de Mallorca. Subjectes: 291 pacients amb diagnòstic d’otitis mitjana aguda en la història clínica electrònica des de novembre de 2015 a maig 2016. Mesures: De la història clínica i la base de dades de prescripció es va obtenir: les característiques sociodemogràfiques i el tractament farmacològic emprat: antibiòtic, antiinflamatoris no esteroides (AINE) o corticoides; via oral o tòpica; descrits amb estadístics de centralitat i dispersió. Las diferències entre OMA i OMA supurada (OMS) es varen contrastar mitjançant Chi-quadrat de Pearson. Resultats: S’analitzaren 249 pacients que compliren els criteris d’inclusió. La mitjana d’edat va ser de 39 anys (DE 13); 102/249 (41%) eren homes. Els antibiòtics orals van ser el principal grup farmacològic prescrit 126 (50,6%), seguit de l’antibiòtic tòpic 118 (47,4%) i corticoide tòpic 102 (41%). Altres fàrmacs emprats foren AINE 71 (28,5%), corticoides nasals 38 (15,3%) i corticoides orals 5 (2%). Els pacients con OMS tenien major probabilitat d’haver rebut antibiòtics tòpics que les no supurades 63,2% vs 40,4% (p=0,002) i més corticoides tòpics 57,4% vs 64,8% (p=0,001). Per a la resta de grups farmacològics ho hi va haver diferències estadísticament significatives. Únicament 34/249 (13,7%) de las OMA valorades presentaren una adequada prescripció farmacològica. Conclusions: En el nostre centre de salut hi ha escassa adherència a les recomanacions terapèutiques actuals de la otitis mitjana aguda, així com un ús inapropiat dels antibiòtics.Objective: To describe the treatment used against acute otitis media (AOM) in adults and adherence to current clinical protocols and guidelines. Design: Cross-sectional and retrospective descriptive study. Setting: Health Center Sa Torre de Manacor in the Health Area of Mallorca. Participants: 291 patients diagnosed with acute otitis media in the electronic clinical record during the period November 2015 - May 2016. Measurements: From primary care electronical clinical records and prescription database we obtained sociodemografic characteristics of patients and prescriptions of antibiotics, non-steroidal anti-inflammatory drugs (NSAID) or steroids in oral or topical use; described by centrality and dispersion statistics. Differences between AOM and suppurative acute otitis media (SOM) were calculated using Pearson’s Chi-square. Results: We analyzed 249 patients who met the inclusion criteria. The mean age was 39 years (SD 13); 102/249 (41%) were males. Oral antibiotics were the main pharmacological group prescribed 126 (50.6%), followed by topical antibiotic 118 (47.4%) and topical corticosteroid 102 (41%). Other drugs were NSAIDs 71 (28.5%), nasal corticosteroids 38 (15.3%) and oral corticosteroids 5 (2%). Patients with SOM were more likely to have received topical antibiotics than AOM 63,2% vs 40,4% (p=0,002) and more topical corticosteroids 57,4% vs 64,8% (p=0,001). For the remaining pharmacological groups there were no statistically significant differences. Only 34/249 (13.7%) of the AOMs assessed had an adequate pharmacological prescription. Conclusions: There is little adherence in our health center to the current therapeutic recommendations of acute otitis media, as well as an inappropriate use of antibiotics

Hypertension is related to the degradation of dietary frying oils

[Background]: The family kitchen resembles an uncontrolled laboratory experiment, and some discrepancies in the relation between the risk of hypertension and dietary fat may be partly due to the manipulation to which the fats were subjected. [Objective]: We investigated whether deterioration in the quality of the cooking oils in the family household contributes to the risk of high blood pressure. [Design]: The study was cross-sectional. Anthropometric measurements were obtained for 1226 persons aged 18–65 y who were selected randomly from the municipal census of Pizarra, Spain. An oral-glucose-tolerance test was given to 1020 of these persons. Samples of the cooking oil being used were taken from the kitchens of a random subset of 538 persons. The concentrations of polar compounds and polymers were used as markers of the deterioration of the oils. The strength of association between variables was measured by calculating the odds ratio from logistic models. [Results]: Hypertension was strongly associated with obesity and was influenced by sex, diabetes, and age. The presence of excess polar compounds in the cooking oil and the use of sunflower oil were related to the risk of hypertension, whereas the concentration of monounsaturated fatty acids in the serum phospholipids was negatively related to this risk. These associations remained after inclusion in the models of age, sex, obesity, and the presence of carbohydrate metabolism disorder. [Conclusions]: The risk of hypertension is positively and independently associated with the intake of cooking oil polar compounds and inversely related to blood concentrations of monounsaturated fatty acids

La construcción de la identidad de género en pacientes transexuales.

Se presenta un estudio de la forma de comienzo y el curso de los síntomas principales de la transexualidad en 200 pacientes pertenecientes a la Unidad de Trastornos de Identidad de Género del HR. Carlos Haya de Málaga (España). El análisis exhaustivo de variables psicopatológicas y sociofamiliares asociadas al trastorno así como las diferencias encontradas entre pacientes hombre-a-mujer y pacientes mujer-a-hombre en el proceso de cambio de sexo, resultan fundamentales para el correcto diagnóstico y abordaje psicoterapéutico de la transexualidad