ERICKA BARBOSA TRARBACH
Projetos de Pesquisa
Unidades Organizacionais
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
31 resultados
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Agora exibindo 1 - 10 de 31
- Cabergoline and prolactinomas: lack of association between DRD2 polymorphisms and response to treatment(2017) BUENO, C. B. F.; TRARBACH, E. B.; BRONSTEIN, M. D.; GLEZER, A.Background About 80% of prolactinomas respond to dopamine agonists (DA) with hormonal normalization and tumor shrinkage. Mechanisms of DA resistance include reduction of dopamine receptor subtype 2 (DRD2) expression, short and long isoform ratio and post-receptor mechanisms. It was suggested that polymorphisms in the gene encoding dopamine receptor subtype 2 gene (DRD2) could be associated with variable effectiveness of cabergoline (CAB). Objective To assess the influence of DRD2 polymorphisms in responsiveness of CAB treatment in patients with prolactinoma. Study design and patients Cross-sectional retrospective case-control study analyzing the frequency of five DRD2 polymorphisms in 148 patients with prolactinoma and 349 healthy subjects. The association of genetic variants and clinical characteristics with CAB responsiveness was performed in 118 patients (mean age at diagnosis 29 years; range 11-61 years) with hormonal evaluation. Patients with prolactin (PRL) normalization were considered as responders. Results No association in genotypes and allele proportions was found comparing patients and controls. On pharmacogenetic study, 118 patients on CAB were included and 20% were non-responders. No association was found between clinical characteristics (gender, age, PRL level and tumor size at diagnosis) and polymorphisms of DRD2 with CAB responsiveness. Otherwise, there was association between polymorphisms rs1076560 (allele A) and rs1800497 (allele T) and the presence of macroadenomas. Conclusion No correlation was found between DRD2 polymorphisms and CAB responsiveness in patients with prolactinoma. More data are necessary in order to assess the influence of DRD2 genotyping on DA treatment response.
- Genetic Predictors of Long-Term Response to Growth Hormone (GH) Therapy in Children With GH Deficiency and Turner Syndrome: The Influence of a SOCS2 Polymorphism(2014) BRAZ, Adriana F.; COSTALONGA, Everlayny F.; TRARBACH, Ericka B.; SCALCO, Renata C.; MALAQUIAS, Alexsandra C.; GUERRA-JUNIOR, Gil; ANTONINI, Sonir R. R.; MENDONCA, Berenice B.; ARNHOLD, Ivo J. P.; JORGE, Alexander A. L.Background: There is great interindividual variability in the response to GH therapy. Ascertaining genetic factors can improve the accuracy of growth response predictions. Suppressor of cytokine signaling (SOCS)-2 is an intracellular negative regulator of GH receptor (GHR) signaling. Objective: The objective of the study was to assess the influence of a SOCS2 polymorphism (rs3782415) and its interactive effect with GHR exon 3 and -202 A/C IGFBP3 (rs2854744) polymorphisms on adult height of patients treated with recombinant human GH (rhGH). Design and Patients: Genotypes were correlated with adult height data of 65 Turner syndrome (TS) and 47 GH deficiency (GHD) patients treated with rhGH, by multiple linear regressions. Generalized multifactor dimensionality reduction was used to evaluate gene-gene interactions. Results: Baseline clinical data were indistinguishable among patients with different genotypes. Adult height SD scores of patients with at least one SOCS2 single-nucleotide polymorphism rs3782415-C were 0.7 higher than those homozygous for the T allele (P < .001). SOCS2 (P < .003), GHR-exon 3 (P = .016) and -202 A/C IGFBP3 (P = .013) polymorphisms, together with clinical factors accounted for 58% of the variability in adult height and 82% of the total height SD score gain. Patients harboring any two negative genotypes in these three different loci (homozygosity for SOCS2 T allele; the GHR exon 3 full-length allele and/or the -202C-IGFBP3 allele) were more likely to achieve an adult height at the lower quartile (odds ratio of 13.3; 95% confidence interval of 3.2-54.2, P = .0001). Conclusion: The SOCS2 polymorphism (rs3782415) has an influence on the adult height of children with TS and GHD after long-term rhGH therapy. Polymorphisms located in GHR, IGFBP3, and SOCS2 loci have an influence on the growth outcomes of TS and GHD patients treated with rhGH. The use of these genetic markers could identify among rhGH-treated patients those who are genetically predisposed to have less favorable outcomes.
- Influence of growth hormone receptor (GHR) exon 3 and-202A/C IGFBP-3 genetic polymorphisms on clinical and biochemical features and therapeutic outcome of patients with acromegaly(2015) JALLAD, Raquel S.; TRARBACH, Ericka B.; DUARTE, Felipe H.; JORGE, Alexander A. L.; BRONSTEIN, Marcello D.The association of GHR-exon 3 and -202 A/C IGFBP3 polymorphisms with clinical presentation, biochemical measurements and response to therapies in acromegaly have been suggested. To evaluate the presence of these polymorphisms in acromegaly and their influence on clinical and laboratorial characteristics of patients at diagnosis and after treatment in a large cohort of acromegalic patients. This is a cross-sectional study developed in a single tertiary reference center. Clinical data were obtained from the medical records of 186 acromegalic patients (116 women, age range 21-88 years). GH and IGF1 levels and GHR-exon 3 and -202 A/C IGFBP3 polymorphisms were evaluated in the same hospital. At diagnosis, serum GH concentrations were lower in patients with GHR-d3 genotype than those with GHR-fl, whereas an association of lower IGFBP3 levels with d3 allele was observed only after neurosurgical or medical treatments. However, these associations were not confirmed in posterior statistical analysis. Our results suggest that GHR-exon 3 and -202 A/C IGFBP3 polymorphisms did not show any consistent association on clinical and laboratorial features of acromegalic patients even after treatment.
bookPart Biologia molecular dos tumores endócrinos(2013) LERARIO, Antonio Marcondes; FRAGOSO, Maria Candida Barisson; BRITO, Luciana Pinto; MARTIN, Regina Matsunaga; TRARBACH, Erika Barbosa; MARUI, Suemi; TOLEDO, Rodrigo de Almeida; DOMENICE, Sorahia; MENDONçA, Berenice Bilharinho de- SOCS2 polymorphisms are not associated with clinical and biochemical phenotypes in acromegalic patients(2017) TRARBACH, Ericka B.; JORGE, Alexander A.; DUARTE, Felipe H.; BRONSTEIN, Marcello D.; JALLAD, Raquel S.Purpose Suppressor of cytokine signaling 2 (SOCS2) is a STAT5b-regulated gene and one of its functions is to influence growth and development through negative regulatory effects on GH/IGF-1 pathway. So, we evaluate the potential influence of SOCS2 single nucleotide polymorphisms (SNPs) on clinical and laboratorial characteristics of a large cohort of Brazilian patients with acromegaly. Methods Four SOCS2 SNPs (rs3782415, rs3816997, rs3825199 and rs11107116) were selected and genotyped by real-time PCR using specific Taqman probe assays. A total of 186 patients (116 women, age range 26-88 years) were evaluated. Results No association of SOCS2 genotypes was observed with none of the following clinical and laboratorial characteristics: age, sex, body mass index, comorbidities, basal GH, oral glucose tolerance test GH nadir, IGF-I, ULNRIGF-I. Conclusion Despite of the key role of SOCS2 in the regulation of GH receptor signaling, we did not find any significant association between SOCS2 polymorphisms and acromegaly.
conferenceObject Molecular Investigation of PTEN and DREAM Genes in Patients with Multinodular Goiter(2014) SHINZATO, Amanda; LERARIO, Antonio M.; DANILOVIC, Debora Lucia Seguro; LIN, Chin Jia; MARUI, Suemi; TRARBACH, Ericka Barbosa- Association between KISS1 rs5780218 promoter polymorphism and onset of growth hormone secreting pituitary adenoma(2019) AMORIM, Paulo V. G. H.; GRANDE, Isabella P. P.; BATISTA, Rafael L.; SILVEIRA, Leticia F. G.; FREIRE, Ane Caroline T. B.; BRONSTEIN, Marcello D.; JALLAD, Raquel S.; TRARBACH, Ericka B.Objectives. - This study analyzed the KISS1 c.-145delA (rs5780218) promoter polymorphism in a cohort of patients with growth hormone secreting pituitary adenoma (somatotropinoma) and controls, to investigate its role in the incidence of acromegaly and to assess patient/tumor characteristics. Material and methods rs5780218 allelic and genotypic distributions were compared between 49 somatotropinoma patients and 167 healthy controls. rs5780218 was also assessed in relation to patient characteristics and tumor aggressiveness, as characterized by tumor invasion and resistance to conventional therapy. The relationship between KISS1 mRNA expression and the rs5780218 genotype was also assessed in available pituitary tumor samples. Results. - The homozygous -/- variant genotype was associated with high rates of somatotropinoma (P < 0.01), but not with tumor invasiveness, patient characteristics or hormonal remission. KISS1 mRNA expression was much lower in somatotropinomas carrying the deleted allele than in homozygous wild type AA. Conclusions. - In this pilot study, the rs5780218 promoter polymorphism was evaluated in pituitary adenoma, and showed a possible association with the incidence of somatotropinoma but not with tumor progression.
- Association Study of GWAS-Derived Loci with Height in Brazilian Children: Importance of MAP3K3, MMP24 and IGF1R Polymorphisms for Height Variation(2015) FONTENELE, Eveline Gadelha Pereira; MORAES, Maria Elisabete Amaral de; D'ALVA, Catarina Brasil; PINHEIRO, Daniel Pascoalino; LANDIM, Sara Aguiar Sales Pinheiro; BARROS, Fernando Antonio de Sousa; TRARBACH, Ericka Barbosa; MENDONCA, Berenice Bilharinho de; JORGE, Alexander Augusto LimaBackground/Aim: The single nucleotide polymorphisms (SNPs) rs2282978 (CDK6), rs2425019 (MMP24), rs8081612 (MAP3K3), rs2871865 (IGF1R) and rs3782415 (SOCS2) were among the SNPs most strongly associated with height in a meta-analysis of 47 genome-wide association studies (GWAS) involving 114,223 adults from six ethnic groups. The present study aimed to examine associations between these SNPs and height in Brazilian children. Methods: Cross-sectional heights of 1,008 healthy unrelated 4.4- to 9.7-year-old children were evaluated. All genotypes were determined by allele-specific polymerase chain reactions. Height standard deviation scores (SDS) were generated for this population and regressed on allele counts. Linear regressions were performed to estimate the effect of individual SNPs or a polygenic allelic score on height. Results: The T allele of rs8081612 (MAP3K3), the C allele of rs2871865 (IGF1R) and the G allele of rs2425019 (MMP24) were significantly associated with a 0.091-SDS greater height (95% CI 0.089-0.093, p = 0.001) by polygenic analysis. The mean height SDS difference between children with 2 'tall' alleles and children with 4 'tall' alleles was 0.24 SDS (95% CI 0.05-0.43, p = 0.01). The observed allelic effect is consistent with that found in previous GWAS. Conclusions: Polymorphisms in MAP3K3, MMP24 and IGF1R act additively on height in children of an admixed population. These results demonstrate the importance of these loci for children's height. (C) 2015 S. Karger AG, Basel
- Cabergoline in the Management of Residual Nonfunctioning Pituitary Adenoma A Single-Center, Open-Label, 2-Year Randomized Clinical Trial(2019) BATISTA, Rafael L.; MUSOLINO, Nina R. C.; CESCATO, Valter A. S.; SILVA, Gilberto O. da; MEDEIROS, Raphael S. S.; HERKENHOFF, Clarissa G. B.; TRARBACH, Ericka B.; CUNHA-NETO, Malebranche B.Background: Complete tumor removal by transsphenoidal surgery is usually difficult for large nonfunctioning pituitary adenomas (NFPAs). A validated medical treatment may be useful for their management. This study evaluates the clinical efficacy of the dopaminergic agonist cabergoline for residual NFPA. Design, Setting, and Participants: We conducted a randomized, parallel, open-label clinical trial that compared cabergoline with nonintervention in patients with residual NFPA after transsphenoidal surgery over 2 years. The primary outcome was clinical efficacy (tumor reduction). The secondary outcome was the relationship between tumor dopamine D2 receptor (D2R) expression and clinical responsiveness. Tumor measurements and clinical evaluations were performed every 6 months. Results: In total, 59 and 57 individuals were randomly assigned to the study and control groups, respectively. At the end of the study, residual tumor shrinkage, stabilization, and enlargement were observed in 28.8%, 66.1%, and 5.1% of patients, respectively, in the medical-therapy group and in 10.5%, 73.7%, and 15.8% of patients, respectively, in the control group (P=0.01). The progression-free survival rate was 23.2 and 20.8 months for the study and control groups, respectively (P=0.01). D2R was not associated with cabergoline responsiveness. No major side effects were related to cabergoline use. Conclusions: Cabergoline was an effective drug for treating residual NFPA, and its use was associated with a high rate of tumor shrinkage ( NCT03271918).
article 0 Citação(ões) na Scopus Nonsense Mutations in FGF8 Gene Causing Different Degrees of Human Gonadotropin-Releasing Deficiency (vol 95, pg 3491, 2010)(2011) TRARBACH, Ericka B.; ABREU, Ana Paula; FERREIRA, Leticia; SILVEIRA, Gontijo; GARMES, Heraldo Mendes; BAPTISTA, Maria TerezaM.; TELES, Milena Gurgel; COSTA, ElaineM. F.; MOHAMMADI, Moosa; PITTELOUD, Nelly; MENDONCA, Berenice B.; LATRONICO, Ana Claudia