A polymorphism in the promoter region of the glucocorticoid receptor gene is associated with its transcriptional activity.
Since glucocorticoid exerts its biological effects by binding to its receptor, the expression efficiency of the glucocorticoid receptor (GR) gene could influence glucocorticoid sensitivity. We found a polymorphism of cytosine/adenine (-22 C/A) in the upstream region of the GR gene. There was no difference in the allelic frequency between normal and type 2 diabetic subjects. The promoter activity determined by luciferase assay was significantly lower in the -22 A allele than in the -22 C allele in both HepG2 (A allele, 4.19 +/- 0.15; C allele, 6.07 +/- 0.27, p < 0.001) and human embryonic kidney 293 cell lines (A allele, 0.93 +/- 0.16; C allele, 1.51 +/- 0.32, p < 0.001). This polymorphism is associated with transcription of the CR gene, which could be related to glucocorticoid sensitivity through an alteration in tissue GR number.
Ikeda
Y
Y
Second Department of Internal Medicine, Kochi Medical School, Japan.
Suehiro
T
T
Tsuzura
S
S
Shiinoki
T
T
Kaneda
T
T
Kumon
Y
Y
Hashimoto
K
K
D000328:Adult; D001483:Base Sequence; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured
D011965:Receptors, Glucocorticoid