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Polymorphisms in genes of GH receptor (GHR) and IGFBP3 in acromegaly: correlation with clinical / laboratory parameters and response to therapy

Grant number: 10/11718-1
Support Opportunities:Regular Research Grants
Duration: December 01, 2010 - November 30, 2012
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Marcello Delano Bronstein
Grantee:Marcello Delano Bronstein
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Acromegaly has variable clinical spectrum ranging from cases with classical symptoms associated with multiple co-morbidities to subclinical or asymptomatic. Generally, the severity of clinical manifestations does not correlate with the degree of GH/IGF-I.The laboratory is characterized by high levels of GH and IGF-I.The dose of GH during the test oral glucose tolerance (OGTT) is considered the gold standard in the assessment of GH secretion, after the diagnosis and treatment of disease. The diagnosis of acromegaly is established by the absence of suppression of GH levels to less than 1 ng/dl in OGTT associated with high levels of IGF-I. However, disagreement between the levels of GH and IGF-.I can be observed. In most cases, there are levels of IGF-I levels associated with GH levels inappropriately high or low normal. Serum IGFBP-3 also show great variability for many years, methodological problems in the dosage of GH have been pointes as responsible for these discrepancies. Currently, the presence of gene polymorphisms in the GH receptor (GHR) and IGFBP3 have been highlighted as a potential alternative explanation for the discrepancies between the levels of GH and IGF-I. Therefore, the objective of this study is to evaluate the influence of genetic factors in hormone levels at diagnosis and after treatment in acromegaly.About 150 patients with acromegaly will be studied. Genomic DNA will be obtained for the study of polymorphisms in genes involved in GH action. The presence or absence of exon 3 in GHR and presence of single nucleotide polymorphisms (-202A/C) in the promoter region of IGFBP-3 will be assessed. The molecular findings are correlated with clinical data and the response to treatment. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TRARBACH, ERICKA B.; JORGE, ALEXANDER A.; DUARTE, FELIPE H.; BRONSTEIN, MARCELLO D.; JALLAD, RAQUEL S.. SOCS2 polymorphisms are not associated with clinical and biochemical phenotypes in acromegalic patients. Pituitary, v. 20, n. 3, p. 319-324, . (10/11718-1)
JALLAD, RAQUEL S.; TRARBACH, ERICKA B.; DUARTE, FELIPE H.; JORGE, ALEXANDER A. L.; BRONSTEIN, MARCELLO D.. 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. Pituitary, v. 18, n. 5, p. 666-673, . (10/11718-1)

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