RESUMO
Ad4BP/SF-1 plays key roles at all levels of the hypothalamic-pituitary-steroidogenic organ axis and its functional disruption causes endocrine disorders of these organs. However, only three human subjects with Ad4BP/SF-1 mutations have been reported to date, suggesting limited clinical significance as a cause of inborn adrenal or sexual abnormalities. We report the first functional characterization of a new variation found in the hinge region of human Ad4BP/SF-1, G146A. Resulting from a single nucleotide shift (GGG-->GCG), G146A bears slightly diminished transactivation activity evidenced by both adrenal specific cyp11A promoter and ovary specific cyp19 promoter II. The variation does not affect protein expression or stability, exhibiting no dominant negative effect. G146A has a normal interaction pattern with standard co-regulators and subnuclear distribution pattern, and can be considered as a nonsynonymous single nucleotide polymorphism, since it occurs in normals and patients with adrenal diseases. In normal Japanese the allele C frequency is 8%, while in a preliminary population of patients with adrenal diseases it is elevated to 30%; suggesting the G146A variation might be of clinical importance.
Assuntos
Doenças das Glândulas Suprarrenais/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Predisposição Genética para Doença/genética , Rim/metabolismo , Polimorfismo Genético/fisiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional/fisiologia , Animais , Povo Asiático , Chlorocebus aethiops , Proteínas de Ligação a DNA/química , Feminino , Fatores de Transcrição Fushi Tarazu , Proteínas de Homeodomínio , Humanos , Masculino , Mutação , Polimorfismo Genético/genética , Estrutura Terciária de Proteína , Receptores Citoplasmáticos e Nucleares , Fator Esteroidogênico 1 , Fatores de Transcrição/químicaRESUMO
Objective To investigate the clinical significance of quantitation of TGF-?1 mRNA of peripheral blood mononuclear cell (PBMC) in type 2 diabetic patients at different stages of nephropathy (DN). Methods TGF-?1 mRNA transcription in PBMC was analyzed quantitatively by RT-PCR and dot blot in 93 cases of type 2 diabetic patients and 35 normal controls. Correlation of TGF-?1 mRNA in PBMC with 24 hours urinary albumin excretion rate (UAER) was also analysed. Results TGF-?1 mRNA level of PBMC in type 2 diabetic patients was significantly higher than that in normal controls (1.56?1.00 vs 1.03?0.25, P
