Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by van Rossum, E. F.C.
Right arrow Articles by Lamberts, S. W.J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van Rossum, E. F.C.
Right arrow Articles by Lamberts, S. W.J.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 51:3128-3134, 2002
© 2002 by the American Diabetes Association, Inc.

A Polymorphism in the Glucocorticoid Receptor Gene, Which Decreases Sensitivity to Glucocorticoids In Vivo, Is Associated With Low Insulin and Cholesterol Levels

Elisabeth F.C. van Rossum1, Jan W. Koper1, Nannette A.T.M. Huizenga1, André G. Uitterlinden1, Joop A.M.J.L. Janssen1, Albert O. Brinkmann2, Diederick E. Grobbee3, Frank H. de Jong1, Cornelia M. van Duyn4, Huibert A.P. Pols1, and Steven W.J. Lamberts1

1 Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
2 Department of Endocrinology & Reproduction, Erasmus Medical Center, Rotterdam, the Netherlands
3 Department of Julius Center, University of Utrecht, Utrecht, the Netherlands
4 Department of Epidemiology & Biostatistics, Erasmus Medical Center, Rotterdam, the Netherlands

We investigated whether a polymorphism in codons 22 and 23 of the glucocorticoid (GC) receptor gene [GAGAGG(GluArg) -> GAAAAG(GluLys)] is associated with altered GC sensitivity, anthropometric parameters, cardiovascular risk factors, and sex steroid hormones. In a subgroup of 202 healthy elderly subjects of the Rotterdam Study, we identified 18 heterozygotes (8.9%) for the 22/23EK allele (ER22/23EK carriers). In the highest age group, the number of ER22/23EK carriers was higher (67–82 years, 12.9%) than in the youngest age group (53–67 years, 4.9%; P < 0.05). Two dexamethasone (DEX) suppression tests with 1 and 0.25 mg DEX were performed, and serum cortisol and insulin concentrations were compared between ER22/23EK carriers and noncarriers. After administration of 1 mg DEX, the ER22/23EK group had higher serum cortisol concentrations (54.8 ± 18.3 vs. 26.4 ± 1.4 nmol/l, P < 0.0001), as well as a smaller decrease in cortisol (467.0 ± 31.7 vs. 484.5 ± 10.3 nmol/l, P < 0.0001). ER22/23EK carriers had lower fasting insulin concentrations (P < 0.001), homeostasis model assessment- insulin resistance (IR) (index of IR, P < 0.05), and total (P < 0.02) and LDL cholesterol concentrations (P < 0.01). Our data suggest that carriers of the 22/23EK allele are relatively more resistant to the effects of GCs with respect to the sensitivity of the adrenal feedback mechanism than noncarriers, resulting in a better metabolic health profile.


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 FASEB J.Home page
R. Donn, A. Berry, A. Stevens, S. Farrow, J. Betts, R. Stevens, C. Clayton, J. Wang, L. Warnock, J. Worthington, et al.
Use of gene expression profiling to identify a novel glucocorticoid sensitivity determining gene, BMPRII
FASEB J, February 1, 2007; 21(2): 402 - 414.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
R. ROSMOND, V. RADULOVIC, and G. HOLM
A Brief Update of Glucocorticoid Receptor Variants and Obesity Risk
Ann. N.Y. Acad. Sci., November 1, 2006; 1083(1): 153 - 164.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. Rautanen, J. G. Eriksson, J. Kere, S. Andersson, C. Osmond, P. Tienari, H. Sairanen, D. J. P. Barker, D. I. W. Phillips, T. Forsen, et al.
Associations of Body Size at Birth with Late-Life Cortisol Concentrations and Glucose Tolerance Are Modified by Haplotypes of the Glucocorticoid Receptor Gene
J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4544 - 4551.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
K. C. M. C. Koeijvoets, E. F. C. van Rossum, G. M. Dallinga-Thie, E. W. Steyerberg, J. C. Defesche, J. J. P. Kastelein, S. W. J. Lamberts, and E. J. G. Sijbrands
A Functional Polymorphism in the Glucocorticoid Receptor Gene and Its Relation to Cardiovascular Disease Risk in Familial Hypercholesterolemia
J. Clin. Endocrinol. Metab., October 1, 2006; 91(10): 4131 - 4136.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
E. H Stolte, B M L. V. van Kemenade, H. F J Savelkoul, and G. Flik
Evolution of glucocorticoid receptors with different glucocorticoid sensitivity.
J. Endocrinol., July 1, 2006; 190(1): 17 - 28.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
G Decorti, S De Iudicibus, G Stocco, S Martelossi, I Drigo, F Bartoli, and A Ventura
Glucocorticoid receptor polymorphisms in inflammatory bowel disease
Gut, July 1, 2006; 55(7): 1053 - 1054.
[Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
J. Majnik, A. Patocs, K. Balogh, M. Toth, P. Gergics, A. Szappanos, A. Mondok, G. Borgulya, P. Panczel, Z. Prohaszka, et al.
Overrepresentation of the N363S Variant of the Glucocorticoid Receptor Gene in Patients with Bilateral Adrenal Incidentalomas
J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2796 - 2799.
[Abstract] [Full Text] [PDF]

Home page
 Sci SignalHome page
G. P. Chrousos and T. Kino
Intracellular Glucocorticoid Signaling: A Formerly Simple System Turns Stochastic
Sci. Signal., October 4, 2005; 2005(304): pe48 - pe48.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
H. Russcher, P. Smit, E. L. T. van den Akker, E. F. C. van Rossum, A. O. Brinkmann, F. H. de Jong, S. W. J. Lamberts, and J. W. Koper
Two Polymorphisms in the Glucocorticoid Receptor Gene Directly Affect Glucocorticoid-Regulated Gene Expression
J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5804 - 5810.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. J.E. Tissing, J. P.P. Meijerink, M. L. den Boer, B. Brinkhof, E. F.C. van Rossum, E. R. van Wering, J. W. Koper, P. Sonneveld, and R. Pieters
Genetic Variations in the Glucocorticoid Receptor Gene Are Not Related to Glucocorticoid Resistance in Childhood Acute Lymphoblastic Leukemia
Clin. Cancer Res., August 15, 2005; 11(16): 6050 - 6056.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
H. Russcher, E. F. C. van Rossum, F. H. de Jong, A. O. Brinkmann, S. W. J. Lamberts, and J. W. Koper
Increased Expression of the Glucocorticoid Receptor-A Translational Isoform as a Result of the ER22/23EK Polymorphism
Mol. Endocrinol., July 1, 2005; 19(7): 1687 - 1696.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
S. WUST, I. S. FEDERENKO, E. F.C. VAN ROSSUM, J. W. KOPER, R. KUMSTA, S. ENTRINGER, and D. H. HELLHAMMER
A Psychobiological Perspective on Genetic Determinants of Hypothalamus-Pituitary-Adrenal Axis Activity
Ann. N.Y. Acad. Sci., December 1, 2004; 1032(1): 52 - 62.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
I. S. Federenko, M. Nagamine, D. H. Hellhammer, P. D. Wadhwa, and S. Wust
The Heritability of Hypothalamus Pituitary Adrenal Axis Responses to Psychosocial Stress Is Context Dependent
J. Clin. Endocrinol. Metab., December 1, 2004; 89(12): 6244 - 6250.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
E. F. C. van Rossum, P. G. Voorhoeve, S. J. te Velde, J. W. Koper, H. A. Delemarre-van de Waal, H. C. G. Kemper, and S. W. J. Lamberts
The ER22/23EK Polymorphism in the Glucocorticoid Receptor Gene Is Associated with a Beneficial Body Composition and Muscle Strength in Young Adults
J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4004 - 4009.
[Abstract] [Full Text] [PDF]

Home page
 Ann. N. Y. Acad. Sci.Home page
E R. DE KLOET
Hormones and the Stressed Brain
Ann. N.Y. Acad. Sci., June 1, 2004; 1018(1): 1 - 15.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Wust, E. F. C. van Rossum, I. S. Federenko, J. W. Koper, R. Kumsta, and D. H. Hellhammer
Common Polymorphisms in the Glucocorticoid Receptor Gene Are Associated with Adrenocortical Responses to Psychosocial Stress
J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 565 - 573.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. Stevens, D. W. Ray, E. Zeggini, S. John, H. L. Richards, C. E. M. Griffiths, and R. Donn
Glucocorticoid Sensitivity Is Determined by a Specific Glucocorticoid Receptor Haplotype
J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 892 - 897.
[Abstract] [Full Text] [PDF]

Home page
 Recent Prog Horm ResHome page
E. F.C. van Rossum and S. W.J. Lamberts
Polymorphisms in the Glucocorticoid Receptor Gene and Their Associations with Metabolic Parameters and Body Composition
Recent Prog. Horm. Res., January 1, 2004; 59(1): 333 - 357.
[Abstract] [Full Text]

Home page
 Ann. N. Y. Acad. Sci.Home page
F. HOLSBOER
High-Quality Antidepressant Discovery by Understanding Stress Hormone Physiology
Ann. N.Y. Acad. Sci., December 1, 2003; 1007(1): 394 - 404.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2002 by the American Diabetes Association.