| Glucocorticoid receptor gene, low-grade inflammation, and heart failure: the Heart and Soul study. | |
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MedLine Citation:
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PMID: 20371666 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CONTEXT: A common haplotype of the glucocorticoid receptor (GR) gene has been associated with increased susceptibility to coronary heart disease (CHD). Whether this haplotype predisposes to heart failure (HF) is unknown. OBJECTIVE: The objective of the study was to determine whether GR haplotype 3 is associated with HF and whether this association is explained by low-grade inflammation (C-reactive protein). DESIGN: In a prospective cohort study, participants were genotyped for common GR gene polymorphisms (ER22/23EK, BclI C/G, N363S, 9beta A/G). Haplotype analyses were conducted. SETTING: The study was conducted at one university medical center, two Veterans Affairs medical centers, and nine public health clinics. PATIENTS: Patients included 526 white outpatients with stable CHD. MAIN OUTCOME MEASURES: Echocardiographic evidence of ventricular dysfunction, self-reported heart failure, and subsequent hospitalization for heart failure were measured. RESULTS: After adjusting for age, sex, smoking, and body mass index, participants with two copies of haplotype 3 were more likely than those with 0 or 1 copy to report heart failure [hazard ratio (HR) 4.15, 95% confidence interval (CI) 1.5-11.3, P < 0.01], have systolic dysfunction (left ventricular ejection fraction <50%) (HR 3.0, 95% CI 0.9-9.9, P = 0.07), and be hospitalized for HF during a mean follow-up of 6 yr (HR 3.0, 95% CI 1.3-7.0, P = 0.01). These associations were attenuated after adjustment for higher C-reactive protein levels in patients with two copies of haplotype 3. CONCLUSIONS: We found that the GR gene haplotype 3 was associated with prevalent HF, systolic dysfunction, and subsequent HF hospitalization in patients with CHD. This association was partly mediated by low-grade inflammation. |
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Authors:
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Christian Otte; Stefan W?st; Shoujun Zhao; Ludmila Pawlikowska; Pui-Yan Kwok; Mary A Whooley |
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Publication Detail:
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Type: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-04-06 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 95 ISSN: 1945-7197 ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-06-07 Completed Date: 2010-07-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: 2885-91 Citation Subset: AIM; IM |
Affiliation:
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Department of Psychiatry, University Medical Center, 20246 Hamburg-Eppendorf, Germany. otte@uke.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aged Biological Markers / blood C-Reactive Protein / metabolism Coronary Disease / genetics, physiopathology Electrocardiography Female Follow-Up Studies Genotype Haplotypes Heart Failure / genetics* Hospitalization / statistics & numerical data Humans Hydrocortisone / urine Inflammation / genetics* Interleukin-6 / metabolism Male Middle Aged Polymorphism, Genetic / genetics Receptors, Glucocorticoid / genetics* Reverse Transcriptase Polymerase Chain Reaction Stroke Volume / physiology Ventricular Dysfunction / genetics, physiopathology |
| Chemical | |
Reg. No./Substance:
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0/Biological Markers; 0/Interleukin-6; 0/Receptors, Glucocorticoid; 50-23-7/Hydrocortisone; 9007-41-4/C-Reactive Protein |
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