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Lookup NU author(s): Dr Akheel Syed, Professor Julie Irving, Dr Chris RedfernORCiD, Dr Andrew Hall, Professor Nigel Unwin, Professor Martin White, Professor Raj Bhopal CBE, Dr Jolanta Weaver
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The glucocorticoid receptor (GR) may be a common link between human obesity/metabolic syndrome and Cushing's syndrome. The effects of glucocorticoids are mediated through the functional isoform, GRα. An alternative isoform, GRβ, behaves as a dominant negative inhibitor of GRα and has been implicated as a contributing factor to glucocorticoid resistance. A naturally occurring ATTTA to GTTTA single nucleotide polymorphism (A3669G) located in the 3′ end of exon 9β results in increased stability of GRβ mRNA and increased GRβ protein expression. Enhanced GRβ expression may result in greater inhibition of GRα transcriptional activity, resulting in glucocorticoid insensitivity. To test the hypothesis that the 3669G allele would result in a phenotype less likely to express features of glucocorticoid excess, we studied the prevalence of this polymorphism and its relationship with obesity and features of the metabolic syndrome in 322 Europid and 262 South-Asian subjects in northeast England. We report evidence that 3669G allele is associated with reduced central obesity in Europid women and a more favorable lipid profile in Europid men. These data suggest that the 3669G allele may attenuate the undesirable effects of glucocorticoids on fat distribution and lipid metabolism, although its penetrance may vary in different ethnic groups. Copyright © 2006 NAASO.
Author(s): Syed, A.A., Irving, J.A.E., Redfern, C.P.F., Hall, A.G., Unwin, N.C., White, M.J.R., Bhopal, R.S., Weaver, J.U.
Publication type: Article
Publication status: Published
Journal: Obesity
Year: 2006
Volume: 14
Issue: 5
Pages: 759-764
Print publication date: 01/05/2006
ISSN (print): 1930-7381
ISSN (electronic): 1930-739X
URL: http://dx.doi.org/10.1038/oby.2006.86
DOI: 10.1038/oby.2006.86
PubMed id: 16855182
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