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(Referência obtida automaticamente do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Modulatory effect of BclI GR gene polymorphisms on the obesity phenotype in Brazilian patients with Cushing's disease

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Autor(es):
Moreira, Ricardo P. P. [1] ; Bachega, Tania A. S. S. [1] ; Machado, Marcio C. [2] ; Mendonca, Berenice B. [1] ; Bronstein, Marcello D. [2] ; Villares Fragoso, Maria Candida B. [1, 2]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Med, Unidade Suprarrenal, Lab Hormonios Genet Mol LIM 42, Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Hosp Clinicas, Disciplina Endocrinol & Metabol, Sao Paulo - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Clinics; v. 68, n. 5, p. 579-585, Maio 2013.
Citações Web of Science: 3
Resumo

OBJECTIVES: Patients with Cushing's disease exhibit wide phenotypic variability in the severity of obesity, diabetes and hypertension. In the general population, several glucocorticoid receptor genes (NR3C1) and HSD11B1 polymorphisms are associated with altered glucocorticoid sensitivity and/or metabolism, resulting in an increased or reduced risk of an adverse metabolic profile. Our aim was to analyze the association of NR3C1 and HSD11B1 gene variants with the severity of some clinical and hormonal features of Cushing's disease. METHODS: Sixty-four patients presenting with Cushing's disease were diagnosed based on adrenocorticotrophic hormone levels, high-dose dexamethasone suppression tests and/or inferior petrosal sinus sampling and magnetic resonance imaging. The A3669G, ER22/23EK, N363S BclI-NR3C1 and HSD11B1-rs12086634 variants were screened. RESULTS: The BclI, HSD11B1-rs12086634 and A3669G variants were found in 36%, 19.5% and 14% of alleles, respectively. The N363S and ER22/23EK polymorphisms were identified in heterozygosis once in only two patients (1.5% of alleles). There were no differences in the weight gain or prevalence of diabetes and hypertension in the patients carrying the abovementioned alleles compared to the wild-type carriers. Interestingly, the mean body mass index (BMI) of the BclI carriers was significantly higher than the non-carriers (34.4±7 kg/m2 vs. 29.6±4.7 kg/m2, respectively). None of the polymorphisms were associated with the basal adrenocorticotrophic hormone, FU levels or F level after dexamethasone suppression testing. CONCLUSION: Although Cushing's disease results from increased glucocorticoid secretion, we observed that interindividual variability in the peripheral glucocorticoid sensitivity, mediated by the glucocorticoid receptor, could modulate the obesity phenotype. (AU)

Processo FAPESP: 09/54394-4 - Análise dos fatores genéticos envolvidos no desenvolvimento da síndrome metabólica durante a terapia com glicocorticóide em pacientes portadores da deficiência da 21-hidroxilase
Beneficiário:Ricardo Paranhos Pires de Moreira
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 09/54238-2 - Análise do efeito modulatório de polimorfismos nos genes CYP3A7, POR e NR3C1 na terapia com glicocorticóide da forma clássica da deficiência da 21-hidroxilase
Beneficiário:Tania Aparecida Sartori Sanchez Bachega
Linha de fomento: Auxílio à Pesquisa - Regular