Background: To study the glucocorticoid receptor (GR) and the associated gene regulation in the pathogenesis of glucocorticoid- induced glaucoma (GIG) in Chinese patients.Methods: The trabecular cells of normal indivi...Background: To study the glucocorticoid receptor (GR) and the associated gene regulation in the pathogenesis of glucocorticoid- induced glaucoma (GIG) in Chinese patients.Methods: The trabecular cells of normal individuals and patients with GIG were cultured in vitro. By using polymerase chain reaction (PCR),gene fragments on GR DNA binding sites of trabecular cells were amplified. The product was detected by gel electrophoresis.Results: The trabecular cells were cultured successfully in normal individuals and patients with GIG in vitro. A single PCR product was obtained in both two groups with the same size of 545 base pairs.Conclusion: There is not any difference in gene on the GR DNA binding sites between normal individuals and patients with GIG. The results suggest the difference in mRNA or other functional genes. Eye Science 1999 ; 15 ; 46 - 50.展开更多
Background Generalized glucocorticoid resistance syndrome is a rare familial or sporadic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. This syndrome is partially caus...Background Generalized glucocorticoid resistance syndrome is a rare familial or sporadic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. This syndrome is partially caused by mutations in human glucocorticoid receptor （hGR） gene. The clinical spectrum of generalized glucocorticoid resistance is broad, ranging from fatigue or no symptoms to severe hypertension with hypokalemic alkalosis. The purpose of this study was to explore the genetic disorder of glucocorticoid resistance syndrome.Methods We identified a 56-year-old male patient diagnosed with generalized glucocorticoid resistance syndrome accompanied with an adrenocortical adenoma. This asymptomatic patient referred to Peking Union Medical College Hospital for treatment of his adrenal incidentaloma. Endocrinological evaluation consistently revealed his elevated serum cortisol level. Total RNA was extracted from the patient＇s peripheral blood mononuclear leukocytes （PBMLs） and entire coding region of hGR alpha was amplified by reverse transcription （RT）-PCR. To confirm the possible mutation identified by sequencing RT-PCR products, genomic DNA sequence of hGR gene from the patient and 50 healthy controls was analyzed by PCR and directly sequencing.Results A heterozygotic （C→T） substitution at nucleotide position of 1667 （exon 5） in GR alpha gene was found in this patient by sequencing of RT-PCR products of hGR gene. This substitution was also identified at genomic DNA level and it was absent in 100 chromosomes from 50 unrelated health controls. This substitution resulted in a threonine to isoleucine substitution （ACT→ATT） at amino acid 556 in the ligand-binding domain of GR alpha. Conclusion Generalized glucocorticoid resistance in this patient might be caused by a novel heterozygotic mutation in the ligand-binding domain of the GR alpha.展开更多
基金by grants from Nature Science Fundation of China Guangdong province (No.39800163 and No.980112)
文摘Background: To study the glucocorticoid receptor (GR) and the associated gene regulation in the pathogenesis of glucocorticoid- induced glaucoma (GIG) in Chinese patients.Methods: The trabecular cells of normal individuals and patients with GIG were cultured in vitro. By using polymerase chain reaction (PCR),gene fragments on GR DNA binding sites of trabecular cells were amplified. The product was detected by gel electrophoresis.Results: The trabecular cells were cultured successfully in normal individuals and patients with GIG in vitro. A single PCR product was obtained in both two groups with the same size of 545 base pairs.Conclusion: There is not any difference in gene on the GR DNA binding sites between normal individuals and patients with GIG. The results suggest the difference in mRNA or other functional genes. Eye Science 1999 ; 15 ; 46 - 50.
文摘Background Generalized glucocorticoid resistance syndrome is a rare familial or sporadic condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. This syndrome is partially caused by mutations in human glucocorticoid receptor （hGR） gene. The clinical spectrum of generalized glucocorticoid resistance is broad, ranging from fatigue or no symptoms to severe hypertension with hypokalemic alkalosis. The purpose of this study was to explore the genetic disorder of glucocorticoid resistance syndrome.Methods We identified a 56-year-old male patient diagnosed with generalized glucocorticoid resistance syndrome accompanied with an adrenocortical adenoma. This asymptomatic patient referred to Peking Union Medical College Hospital for treatment of his adrenal incidentaloma. Endocrinological evaluation consistently revealed his elevated serum cortisol level. Total RNA was extracted from the patient＇s peripheral blood mononuclear leukocytes （PBMLs） and entire coding region of hGR alpha was amplified by reverse transcription （RT）-PCR. To confirm the possible mutation identified by sequencing RT-PCR products, genomic DNA sequence of hGR gene from the patient and 50 healthy controls was analyzed by PCR and directly sequencing.Results A heterozygotic （C→T） substitution at nucleotide position of 1667 （exon 5） in GR alpha gene was found in this patient by sequencing of RT-PCR products of hGR gene. This substitution was also identified at genomic DNA level and it was absent in 100 chromosomes from 50 unrelated health controls. This substitution resulted in a threonine to isoleucine substitution （ACT→ATT） at amino acid 556 in the ligand-binding domain of GR alpha. Conclusion Generalized glucocorticoid resistance in this patient might be caused by a novel heterozygotic mutation in the ligand-binding domain of the GR alpha.
