9β Polymorphism of the glucocorticoid receptor gene appears to have limited impact in patients with Addison's disease.
BACKGROUND
Addison's disease (AD) has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9β polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD.


METHODS
147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction.


RESULTS
Genotype data for the 9β polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003), increased triglycerides (p = 0.002), reduced HDLC (p<0.001) an elevated highly sensitive C-reactive protein (p = 0.01), compared with controls. The 9β polymorphism (at least one G allele) was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism.


CONCLUSIONS
This study did not identify any associations between the 9β polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD.
Division of Endocrinology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Ian Louis
IL
Ross
Department of Human Genetics, University of Cape Town, Cape Town, South Africa.
Collet
C
Dandara
Department of Human Genetics, University of Cape Town, Cape Town, South Africa.
Marelize
M
Swart
Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa.
Miguel
M
Lacerda
Department of Paediatrics, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
Desmond
D
Schatz
Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Dirk Jacobus
DJ
Blom
D000224:Addison Disease / Q000188:drug therapy / Q000235:genetics*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D002318:Cardiovascular Diseases / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D012307:Risk Factors
D000893:Anti-Inflammatory Agents; D011965:Receptors, Glucocorticoid; D006854:Hydrocortisone