Document Detail


A functional polymorphism in renalase (Glu37Asp) is associated with cardiac hypertrophy, dysfunction, and ischemia: data from the heart and soul study.
MedLine Citation:
PMID:  20975995     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Renalase is a soluble enzyme that metabolizes circulating catecholamines. A common missense polymorphism in the flavin-adenine dinucleotide-binding domain of human renalase (Glu37Asp) has recently been described. The association of this polymorphism with cardiac structure, function, and ischemia has not previously been reported.
METHODS: We genotyped the rs2296545 single-nucleotide polymorphism (Glu37Asp) in 590 Caucasian individuals and performed resting and stress echocardiography. Logistic regression was used to examine the associations of the Glu37Asp polymorphism (C allele) with cardiac hypertrophy (LV mass>100 g/m2), systolic dysfunction (LVEF<50%), diastolic dysfunction, poor treadmill exercise capacity (METS<5) and inducible ischemia.
RESULTS: Compared with the 406 participants who had GG or CG genotypes, the 184 participants with the CC genotype had increased odds of left ventricular hypertrophy (OR = 1.43; 95% CI 0.99-2.06), systolic dysfunction (OR = 1.72; 95% CI 1.01-2.94), diastolic dysfunction (OR = 1.75; 95% CI 1.05-2.93), poor exercise capacity (OR = 1.61; 95% CI 1.05-2.47), and inducible ischemia (OR = 1.49, 95% CI 0.99-2.24). The Glu37Asp (CC genotype) caused a 24-fold decrease in affinity for NADH and a 2.3-fold reduction in maximal renalase enzymatic activity.
CONCLUSIONS: A functional missense polymorphism in renalase (Glu37Asp) is associated with cardiac hypertrophy, ventricular dysfunction, poor exercise capacity, and inducible ischemia in persons with stable coronary artery disease. Further studies investigating the therapeutic implications of this polymorphism should be considered.
Authors:
Ramin Farzaneh-Far; Gary V Desir; Beeya Na; Nelson B Schiller; Mary A Whooley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-20
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-10-26     Completed Date:  2011-03-07     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e13496     Citation Subset:  IM    
Affiliation:
Division of Cardiology, San Francisco General Hospital, San Francisco, California, United States of America. rfarzanehfar@medicine.ucsf.edu
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MeSH Terms
Descriptor/Qualifier:
Aged
Aspartic Acid / chemistry*
Cardiomegaly / genetics*
Female
Glutamic Acid / chemistry*
Humans
Male
Middle Aged
Monoamine Oxidase / chemistry,  genetics*
Myocardial Ischemia / genetics*
Polymorphism, Single Nucleotide*
Prospective Studies
Grant Support
ID/Acronym/Agency:
R01 HL079235/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
56-84-8/Aspartic Acid; 56-86-0/Glutamic Acid; EC 1.4.3.4/Monoamine Oxidase; EC 1.4.3.4./renalase
Comments/Corrections

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