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Investigation of glucocorticoid receptor polymorphisms in relation to metabolic parameters in Addison's disease
- Ross, I. L. (author)
- Levitt, N. S. (author)
- Van der Merwe, L. (author)
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- Schatz, D. A. (author)
- Dandara, C. (author)
- Pillay, T. S. (author)
- Blom, D. J. (author)
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- (creator_code:org_t)
- 2013
- 2013
- English.
- In: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 168, s. 403-412
- Journal article (peer-reviewed)
Abstract
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- Background Uncertainty exists whether glucocorticoid receptor (GCR) polymorphisms play a role in steroid-related side effects in Addison's disease (AD) patients on hydrocortisone. The polymorphisms Bcll and N363S appear to increase sensitivity to cortisol, while the ER22/23EK polymorphism has been associated with resistance to cortisol. Method One hundred and forty seven AD patients, and gender, and ethnicity-matched controls were recruited in South Africa. Three polymorphisms in the GCR were studied, using PCR followed by restriction fragment length analysis. Associations with BMI, lipids, glucose and inflammatory markers were investigated. Results In both patients and controls, the Bcll polymorphism occurred more frequently in whites than in other ethnic groups studied but was not associated with any of the metabolic parameters tested. The ER22/23EK polymorphism was associated with an increased BMI in both patients (29.4 vs 24.7kg/m2) and control subjects (26.3 vs 24.2kg/m2). The ER22/23EK polymorphism was also associated with lower LDL cholesterol in control subjects (3.46 vs 3.93mmol/l) and in patients (3.52 vs 4.10mmol/l). N363S was associated with increased BMI in controls 29.9kg/m2 vs wild type 24.8kg/m2. Median hydrocortisone doses were greater in patients heterozygous for either ER22/23EK 30.0mg or N363S 25.0mg polymorphisms than in wild type patients 20.0mg (both comparisons). Conclusion Alterations in lipids, BMI and hydrocortisone dose were associated with two polymorphisms. Further larger studies are warranted to corroborate these findings.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- low-density-lipoprotein
- bone-mineral density
- inflammatory-bowel-disease
- c-reactive protein
- er22/23ek polymorphism
- cardiovascular-disease
- adrenal insufficiency
- rheumatoid-arthritis
- replacement therapy
- bcli polymorphism
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Pillay, T. S.
- Blom, D. J.
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- University of Gothenburg
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