Subjects homozygous for the BCL1 polymorphism of glucocorticoid receptor gene may have an increased risk for impaired endothelial function
Kimon Stamatelopoulos2, Katerina Saltiki1,3, Emily Mantzou3, Paraskevi Voidonikola2, Christos Papamichael2 & Maria Alevizaki1,3
Objectives: Glucocorticoids may affect cardiovascular risk. Polymorphisms in the glucocorticoid receptor (GlucR) gene have been associated with increased risk for cardiovascular disease. We investigated whether the common Bcl1 polymorphism of the GlucR gene (associated with increased sensitivity to glucocorticoids) may be associated with early markers of atherosclerosis.
Methods: Two hundred and fourteen middle aged apparently healthy subjects (age … 46.8±8.8, BMI 27.2±4.8, 45.4% males) attending a preventive medicine program were examined for unrecognised features of the metabolic syndrome and early indices of cardiovascular disease. BMI, waist and hip circumference, basal cortisol levels, insulin, glucose and lipids were measured. A detailed vascular examination was performed including evaluation of flow mediated dilatation (FMD) and carotid intima media thickness (IMT).
Results: The prevalence of the Bcl1 polymorphism was 26.6% (52.8% wild type, 41.2% heterozygous and 6.0% homozygous for the variance). Homozygous subjects had a significantly lower FMD compared to wild type or heterozygous subjects P=0.029). FMD quartiles were calculated. In logistic regression analysis homozygocity for the Bcl1 polymorphism and LDL levels were the only parameters that remained significant when other confounding factors, which might influence FMD such as age, arterial pressure, smoking, were taken into account. We found that homozygous subjects had a 3.5 higher risk to belong to the lowest FMD quartile compared to heterozygous or wild type subjects (CI: 1.111.5, P=0.035). No significant differences were found in IMT between the various genotypes. No differences were found in BMI, WHR, cortisol, insulin, glucose, lipid levels, HOMA-IR index and arterial pressure between the 3 groups.
Conclusions: The Bcl1 polymorphisms of the GlucR gene may be associated with impaired endothelial function, which is an early marker of atherosclerosis. This finding may imply that increased sensitivity to GC might be implicated in this process.