BclI glucocorticoid receptor polymorphism in relation to cardiovascular variables: the Hoorn and CODAM studies

D. van Moorsel, M.M.J. van Greevenbroek, N.C. Schaper, R.M.A. Henry, C.C. Geelen, E.F.C. van Rossum, G. Nijpels, L.M. 't Hart, C.G. Schalkwijk, C.J.H. van der Kallen, H.P. Sauerwein, J.M. Dekker, C.D.A. Stehouwer, B. Havekes

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Abstract

OBJECTIVE: Excess glucocorticoids are known to cause hypertension and cardiovascular disease (CVD). The BclI glucocorticoid receptor (GR) polymorphism increases glucocorticoid sensitivity and is associated with adverse metabolic effects. Previous studies investigating cardiovascular implications have shown inconsistent results. Therefore, the aim of the present study was to investigate the association of the BclI polymorphism with blood pressure, atherosclerosis, low-grade inflammation, endothelial dysfunction, and prevalent CVD. DESIGN: Observational cohort study, combining two cohort studies designed to investigate genetic and metabolic determinants of CVD. METHODS: We genotyped 1228 individuals (aged 64.7 years+/-8.5) from the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study and Hoorn study for the BclI polymorphism. We measured blood pressure, ankle-brachial index (ABI), and carotid intima-media thickness (cIMT). Low-grade inflammation and endothelial dysfunction scores were computed by averaging Z-scores of six low-grade inflammation markers and four endothelial dysfunction markers respectively. Prevalent CVD was assessed with questionnaires, hospital records, ECG, and ABI. RESULTS: Homozygous carriers (GG) had higher mean arterial pressure (103.8+/-12.4 mmHg vs 101.6+/-12.2 mmHg (mean+/-S.D.); P<0.05) compared with non-carriers (CC). Homozygous carriers had lower ABI compared with heterozygous carriers (CG) (1.08+/-0.13 vs 1.11+/-0.14; P<0.05). After adjustment for all covariates in the full model, the association with ABI was no longer significant. BclI was not associated with systolic blood pressure, cIMT, low-grade inflammation, endothelial dysfunction, and prevalent CVD. CONCLUSIONS: The BclI polymorphism of the GR gene may contribute to an unfavorable cardiovascular profile; however, the effects on cardiovascular variables appear to be limited and partly mediated by the metabolic phenotype exerted by BclI.
Original languageEnglish
Pages (from-to)455-464
JournalEuropean Journal of Endocrinology
Volume173
Issue number4
DOIs
Publication statusPublished - 1 Jan 2015

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