Document Detail


Usefulness of the aldosterone synthase gene polymorphism C-344-T to predict cardiac remodeling in African-Americans versus non-African-Americans with chronic systolic heart failure.
MedLine Citation:
PMID:  17631084     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A common polymorphism exists for the aldosterone synthase (CYP11B2) gene at position 344 (C-344-T). The 344-C allele has been associated with increased aldosterone synthase activity. We hypothesized that the aldosterone synthase gene polymorphism is associated with adverse cardiac remodeling in an ambulatory, chronic heart failure population. The CYP11B2 C-344T genotype was determined in 104 patients with heart failure who were in New York Heart Association classes I to IV, had left ventricular ejection fractions <40%, and were prospectively recruited from an urban heart failure clinic (65% African-American, 69% had a nonischemic cause, with a mean left ventricular ejection fraction of 22 +/- 9%). The 344-C allele frequency was 0.34 (45.2% TT, 42.3% CT, and 12.5% CC) and was significantly lower in African-American (0.27) versus Non-African-American patients (0.44, p = 0.018). Baseline and 1-year follow-up echocardiograms were obtained in 74 patients. Improvement was defined as a decrease in left ventricular end-systolic diameter (LVESD). At follow-up, the 344-C allele was associated with improved LVESD (p = 0.013). In addition, analysis by race showed that this effect was observed only in African-American patients (p <0.006). In multivariate logistic regression, controlling for cause, gender, and spironolactone use, the TT genotype (i.e., absence of 344-C allele) was associated with a fivefold lower rate of improvement in LVESD in African-Americans (p = 0.014). In conclusion, the 344-C allele of the aldosterone synthase gene polymorphism was associated with improved cardiac remodeling over time for African-Americans with chronic systolic heart failure. Although this genetic-driven increase in aldosterone activity should predispose to worse cardiac remodeling, it may represent a more susceptible state and enhanced response to therapy in this racial subgroup.
Authors:
Andreia Biolo; Tania Chao; Toni-Ann S Duhaney; Eugene Kotlyar; Donald Allensworth-Davies; Joseph Loscalzo; Flora Sam
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2007-06-04
Journal Detail:
Title:  The American journal of cardiology     Volume:  100     ISSN:  0002-9149     ISO Abbreviation:  Am. J. Cardiol.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-16     Completed Date:  2007-09-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0207277     Medline TA:  Am J Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  285-90     Citation Subset:  AIM; IM    
Affiliation:
Cardiovascular Section and Evans Department of Medicine, Boston University School of Public Health, Boston, Massachusetts, USA.
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MeSH Terms
Descriptor/Qualifier:
African Americans / genetics*
Aldosterone / physiology
Aldosterone Synthase / genetics*
Alleles
Chronic Disease
Echocardiography
Female
Heart Failure / genetics,  physiopathology*
Humans
Male
Middle Aged
Polymorphism, Genetic*
Prospective Studies
Stroke Volume
Ventricular Remodeling*
Grant Support
ID/Acronym/Agency:
HL079099/HL/NHLBI NIH HHS; K23-HL-04423/HL/NHLBI NIH HHS; M01 RR00533/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
52-39-1/Aldosterone; EC 1.14.15.4/Aldosterone Synthase

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


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