Document Detail

Hypertrophy-associated polymorphisms ascertained in a founder cohort applied to heart failure risk and mortality.
MedLine Citation:
PMID:  21348951     Owner:  NLM     Status:  MEDLINE    
A three-stage approach was undertaken using genome-wide, case-control, and case-only association studies to identify genetic variants associated with heart failure mortality. In an Amish founder population (n = 851), cardiac hypertrophy, a trait integral to the adaptive response to failure, was found to be heritable (h² = 0.28, p = 0.0002) and GWAS revealed 21 candidate hypertrophy SNPs. In a case (n = 1,610)-control (n = 463) study in unrelated Caucasians, one of the SNPs associated with hypertrophy (rs2207418, p = 8 × 10⁻⁶), was associated with heart failure, RR = 1.85(1.25-2.73, p = 0.0019). In heart failure cases rs2207418 was associated with increased mortality, HR = 1.51(1.20-1.97, p = 0.0004). There was consistency between studies, with the GG allele being associated with increased ventricular mass (~13 g/m²) in the Amish, heart failure risk, and heart failure mortality. This SNP is in a gene desert of chromosome 20p12. Five genes are within 2.0 mbp of rs2207418 but with low LD between their SNPs and rs2207418. A region near this SNP is highly conserved in multiple vertebrates (lod score = 1,208). This conservation and the internal consistency across studies suggests that this region has biologic importance in heart failure, potentially acting as an enhancer or repressor element. rs2207418 may be useful for predicting a more progressive form of heart failure that may require aggressive therapy.
Afshin Parsa; Yen-Pei C Chang; Reagan J Kelly; Mary C Corretti; Kathleen A Ryan; Shawn W Robinson; Stephen S Gottlieb; Sharon L R Kardia; Alan R Shuldiner; Stephen B Liggett
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Clinical and translational science     Volume:  4     ISSN:  1752-8062     ISO Abbreviation:  Clin Transl Sci     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-02-25     Completed Date:  2011-06-06     Revised Date:  2013-04-16    
Medline Journal Info:
Nlm Unique ID:  101474067     Medline TA:  Clin Transl Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17-23     Citation Subset:  IM    
Copyright Information:
© 2011 Wiley Periodicals, Inc.
Department of Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA.
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MeSH Terms
Aged, 80 and over
Base Sequence
Cardiomegaly / complications*,  genetics*,  ultrasonography
Cohort Studies
Ethnic Groups / genetics
Founder Effect*
Genetic Predisposition to Disease*
Heart Failure / complications,  genetics*,  mortality*,  ultrasonography
Heart Ventricles / pathology
Middle Aged
Organ Size
Polymorphism, Single Nucleotide / drug effects*,  genetics
Risk Factors
Sequence Homology, Nucleic Acid
Short Interspersed Nucleotide Elements / genetics
Young Adult
Grant Support

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

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