Abstract
BackgroundAddison’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.Materials and Methods147 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.ResultsGenotype 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.ConclusionsThis 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.
Highlights
Addison’s disease (AD) has been associated with an up to twofold increased mortality rate from cardiovascular disease [1,2]
AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense low density lipoprotein (LDL) (p = 0.003), increased triglycerides (p = 0.002), reduced high density lipoprotein cholesterol (HDLC) (p,0.001) an elevated highly sensitive C-reactive protein (p = 0.01), compared with controls
Ross et al previously studied the effects of the above polymorphisms in patients with AD and found that the ER22/ 23EK polymorphism was counter-intuitively associated with an increased BMI, but lower LDL-cholesterol
Summary
Addison’s disease (AD) has been associated with an up to twofold increased mortality rate from cardiovascular disease [1,2]. Previously reported that patients with AD had higher triglycerides (TG), lower high density lipoprotein cholesterol (HDLC), a preponderance of small dense low density lipoprotein (LDL) particles and raised high sensitivity C-reactive protein (hsCRP) compared with healthy controls. These findings may in part account for the increased rates of cardiovascular disease seen in patients with AD [4]. The 9b 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
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