Dirk van Moorsel1, Marleen M J van Greevenbroek1, Nicolaas C Schaper1, Ronald M A Henry1, Charlotte C Geelen2, Elisabeth F C van Rossum2, Giel Nijpels2, Leen M 't Hart1, Casper G Schalkwijk1, Carla J H van der Kallen1, Hans P Sauerwein1, Jacqueline M Dekker2, Coen D A Stehouwer1, Bas Havekes1. 1. Department of Internal MedicineDivision of Endocrinology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The NetherlandsDepartment of Internal MedicineMaastricht University Medical Center, 6202 AZ Maastricht, The NetherlandsAdelante Center of Expertise in Rehabilitation and Audiology6432 CC Adelante, Hoensbroek, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The NetherlandsDepartment of Epidemiology and Biostatistics and the EMGO Institute for Health and Care ResearchVU University Medical Center, 1007 MB Amsterdam, The NetherlandsDepartment of Molecular Cell BiologyLeiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Human BiologyMaastricht University Medical Center, 6200 MD Maastricht, The NetherlandsSection Molecular EpidemiologyLeiden University Medical Center, 2300 RC Leiden, The NetherlandsSchool of Nutrition and Translational Research in Metabolism (NUTRIM)Maastricht, The NetherlandsSchool for Cardiovascular Diseases Maastricht (CARIM)Maastricht, The Netherlands andSchool for Public Health and Primary Care (CAPHRI)Maastricht, The Netherlands Department of Internal MedicineDivision of Endocrinology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The NetherlandsDepartment of Internal MedicineMaastricht University Medical Center, 6202 AZ Maastricht, The NetherlandsAdelante Center of Expertise in Rehabilitation and Audiology6432 CC Adelante, Hoensbroek, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The NetherlandsDepartment of Epidemiology and Biostatistics and the EMGO Institute for Health and Care ResearchVU University Medical Center, 1007 MB Amsterdam, The NetherlandsDepartment of Molecular Cell BiologyLeiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Human BiologyMaastricht 2. Department of Internal MedicineDivision of Endocrinology, Maastricht University Medical Center, PO Box 5800, 6202 AZ Maastricht, The NetherlandsDepartment of Internal MedicineMaastricht University Medical Center, 6202 AZ Maastricht, The NetherlandsAdelante Center of Expertise in Rehabilitation and Audiology6432 CC Adelante, Hoensbroek, The NetherlandsDepartment of Internal MedicineDivision of Endocrinology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The NetherlandsDepartment of Epidemiology and Biostatistics and the EMGO Institute for Health and Care ResearchVU University Medical Center, 1007 MB Amsterdam, The NetherlandsDepartment of Molecular Cell BiologyLeiden University Medical Center, 2300 RC Leiden, The NetherlandsDepartment of Human BiologyMaastricht University Medical Center, 6200 MD Maastricht, The NetherlandsSection Molecular EpidemiologyLeiden University Medical Center, 2300 RC Leiden, The NetherlandsSchool of Nutrition and Translational Research in Metabolism (NUTRIM)Maastricht, The NetherlandsSchool for Cardiovascular Diseases Maastricht (CARIM)Maastricht, The Netherlands andSchool for Public Health and Primary Care (CAPHRI)Maastricht, The Netherlands.
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.
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.
Authors: Robin Lengton; Anand M Iyer; Eline S van der Valk; Ellen K Hoogeveen; Onno C Meijer; Bibian van der Voorn; Elisabeth F C van Rossum Journal: Obes Rev Date: 2021-11-27 Impact factor: 10.867