ERICKA BARBOSA TRARBACH
Projetos de Pesquisa
Unidades Organizacionais
LIM/25 - Laboratório de Endocrinologia Celular e Molecular, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
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- 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.
- FGFR1 and PROKR2 rare variants found in patients with combined pituitary hormone deficiencies(2015) CORREA, Fernanda A.; TRARBACH, Ericka B.; TUSSET, Cintia; LATRONICO, Ana Claudia; MONTENEGRO, Luciana R.; CARVALHO, Luciani R.; FRANCA, Marcela M.; OTTO, Aline P.; COSTALONGA, Everlayny F.; BRITO, Vinicius N.; ABREU, Ana Paula; NISHI, Mirian Y.; JORGE, Alexander A. L.; ARNHOLD, Ivo J. P.; SIDIS, Yisrael; PITTELOUD, Nelly; MENDONCA, Berenice B.The genetic aetiology of congenital hypopituitarism (CH) is not entirely elucidated. FGFR1 and PROKR2 loss-of-function mutations are classically involved in hypogonadotrophic hypogonadism (HH), however, due to the clinical and genetic overlap of HH and CH; these genes may also be involved in the pathogenesis of CH. Using a candidate gene approach, we screened 156 Brazilian patients with combined pituitary hormone deficiencies (CPHD) for loss-of-function mutations in FGFR1 and PROKR2. We identified three FGFR1 variants (p.Arg448Trp, p.Ser107Leu and p.Pro772Ser) in four unrelated patients (two males) and two PROKR2 variants (p. Arg85Cys and p. Arg248Glu) in two unrelated female patients. Five of the six patients harbouring the variants had a first-degree relative that was an unaffected carrier of it. Results of functional studies indicated that the new FGFR1 variant p.Arg448Trp is a loss-of-function variant, while p.Ser107Leu and p.Pro772Ser present signalling activity similar to the wild-type form. Regarding PROKR2 variants, results from previous functional studies indicated that p.Arg85Cys moderately compromises receptor signalling through both MAPK and Ca2+ pathways while p.Arg248Glu decreases calcium mobilization but has normal MAPK activity. The presence of loss-of-function variants of FGFR1 and PROKR2 in our patients with CPHD is indicative of an adjuvant and/or modifier effect of these rare variants on the phenotype. The presence of the same variants in unaffected relatives implies that they cannot solely cause the phenotype. Other associated genetic and/or environmental modifiers may play a role in the aetiology of this condition.