The N363S Polymorphism of the Glucocorticoid Receptor: Potential Contribution to Central Obesity in Men and Lack of Association with Other Risk Factors for Coronary Heart Disease and Diabetes Mellitus1
Considerable evidence suggests that diabetes mellitus and hypertension are influenced by genetic factors. Studies in humans have associated glucocorticoid receptor (GR) polymorphisms with high blood pressure, insulin sensitivity, body mass index, increased visceral fat, and variations in tissue-spec...
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Published in | The journal of clinical endocrinology and metabolism Vol. 86; no. 5; pp. 2270 - 2274 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Endocrine Society
01.05.2001
|
Online Access | Get full text |
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Summary: | Considerable evidence suggests that diabetes mellitus and hypertension
are influenced by genetic factors. Studies in humans have associated
glucocorticoid receptor (GR) polymorphisms with high blood pressure,
insulin sensitivity, body mass index, increased visceral fat, and
variations in tissue-specific steroid sensitivity. The N363S
polymorphism of the GR results in an asparagine to serine amino acid
substitution in a modulatory region of the receptor. Phosphorylation of
serine residues in this region has been shown to enhance
transactivation of GR responsive genes. The aim of this study was to
investigate the association between the 363S allele and
risk factors for coronary heart disease and diabetes mellitus in a
population of European origin living in the northeast of the United
Kingdom. Blood samples from 135 males and 240 females were
characterized for 363 allele status. The overall
frequency of the 363S allele was 3.0%, 23 heterozygotes
(7 males and 16 females) but no 363S homozygotes were
identified. The data show a significant association of the
363S allele with increased waist to hip ratio in males
but not females. This allele was not associated with blood pressure,
body mass index, serum cholesterol, triglycerides, low-density
lipoprotein and high-density lipoprotein cholesterol levels, and
glucose tolerance status. The results of this study suggest that this
GR polymorphism may contribute to central obesity in men. Further
studies are required to elucidate the properties of GR363S
at a molecular level. |
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ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.86.5.7465 |