Document Detail


Glucocorticoid receptor gene, low-grade inflammation, and heart failure: the Heart and Soul study.
MedLine Citation:
PMID:  20371666     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Christian Otte; Stefan W?st; Shoujun Zhao; Ludmila Pawlikowska; Pui-Yan Kwok; Mary A Whooley
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Publication Detail:
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:
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:
Created Date:  2010-06-07     Completed Date:  2010-07-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2885-91     Citation Subset:  AIM; IM    
Affiliation:
Department of Psychiatry, University Medical Center, 20246 Hamburg-Eppendorf, Germany. otte@uke.de
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MeSH Terms
Descriptor/Qualifier:
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:
0/Biological Markers; 0/Interleukin-6; 0/Receptors, Glucocorticoid; 50-23-7/Hydrocortisone; 9007-41-4/C-Reactive Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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