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(Hypertension. 2003;41:404.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Association of Coronary Artery Disease With Glucocorticoid Receptor N363S Variant

From the Basic & Clinical Genomics Laboratory, Department of Physiology and Institute for Biomedical Research, The University of Sydney (R.C.Y.L., B.J.M.), NSW; Cardiovascular Genetics Laboratory, Prince of Wales Hospital, Centre for Thrombosis and Vascular Research, University of New South Wales (X.L.W.), Sydney, NSW; and Southwest Foundation for Biomedical Research (X.L.W.), San Antonio, Tex.

Correspondence to Brian J. Morris, DSc, Basic & Clinical Genomics Laboratory, Department of Physiology and Institute for Biomedical Research, Building F13, The University of Sydney, NSW 2006, Australia. E-mail brianm{at}physiol.usyd.edu.au

Overweight is associated with the N363S variant in the glucocorticoid receptor (encoded by nuclear receptor subfamily 3, group C, member 1 gene: NR3C1). The present study examined whether the N363S polymorphism might also be associated with coronary artery disease (CAD). This involved 556 patients with CAD, of which 437 were analyzed, and 302 control subjects, all being of Anglo-Celtic descent residing in Sydney. An extensive range of phenotypic parameters was collected from the patients, and leukocyte DNA from all subjects was genotyped by polymerase chain reaction–restriction fragment length polymorphism analysis for the A1218G (N363S) variant. Frequency of the S363 allele was 0.04 in healthy normal-weight control subjects but was 0.15 in patients with CAD (P=2.0x10^-5) and was also elevated in subjects with CAD who were not overweight (0.14) (P=2.6x10^-5), supporting a primary association with CAD. Frequency of S363 allele carriers in subjects with CAD who had angina was particularly high: unstable angina (0.45), stable angina (0.29), and no angina (0.26) (P for trend=0.016). Elevated cholesterol (P=0.027), triglycerides (P=0.005), and total cholesterol/HDL ratio (P=0.011), after Bonferroni, tracked with the S363 allele, consistent with accentuation of mechanisms that predispose to atheroma formation in coronary vessels. The data suggest a role for glucocorticoid receptor variation in the underlying cause of CAD.

Key Words: glucocorticoids • genetics • coronary artery disease • population

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