Glucocorticoid receptor gene and risk of cardiovascular disease

Archives of Internal Medicine
Erica L T van den AkkerSteven W J Lamberts

Abstract

Genetic variants in immunomodulating genes have been suggested to contribute to the risk of cardiovascular disease. Glucocorticoids are important regulators of inflammatory processes and the immune system. Our aim was to determine the contribution of genetic glucocorticoid receptor variants, with different cortisol sensitivities, to the risk of cardiovascular disease. The study was conducted in a large (n=7983) population-based, prospective cohort of the Rotterdam Study. The mean duration of follow-up was 8.9 years. Measures of cardiovascular disease were incident myocardial infarction, coronary heart disease, high-sensitivity C-reactive protein level, interleukin 6 level, and arteria carotis intima-media thickness. Persons homozygous for haplotype 3, which is a common variant of the glucocorticoid receptor gene, had a more than 2-fold increased risk of myocardial infarction (hazard ratio, 2.1; 95% confidence interval, 1.13-4.07) and an almost 3-fold increased risk of coronary heart disease (hazard ratio, 2.6; 95% confidence interval, 1.40-4.81) compared with nonhomozygous persons. In addition, their C-reactive protein and interleukin 6 levels were higher, and carotis intima-media thickness was greater. No associations were fou...Continue Reading

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