Document Detail

Association of the peroxisome proliferator-activated receptor α gene L162V polymorphism with stage C heart failure.
MedLine Citation:
PMID:  21430558     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To analyze whether genetic variants of PPARA are associated with the development of stage C heart failure.
METHODS: We analyzed the distribution of the rs1800206, rs4253778 and rs135551 polymorphisms in genomic DNA extracted from peripheral blood cells of 534 patients in different heart failure stages and 63 healthy individuals. The mRNA expression of the peroxisome proliferator-activated receptor (PPAR)α target genes long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and medium-chain acyl-CoA dehydrogenase (MCAD) was measured in myocardial biopsies of a subgroup of stage B and C patients. Functional studies were performed in HL-1 cardiomyocytes.
RESULTS: The V162 allele of the rs1800206 polymorphism was more frequent in stage C patients than in stage A and B patients and healthy individuals. Patients with the V162 allele exhibited decreased myocardial LCHAD and MCAD mRNA expression as compared to L162 homozygote patients. In addition, stage C patients exhibited lower myocardial LCHAD and MCAD mRNA expression than stage B patients. Cardiomyocytes transfected with the V162 allele presented decreased PPARα transcriptional activity, LCHAD mRNA expression and ATP production compared to cardiomyocytes transfected with the L162 variant.
CONCLUSIONS: These findings suggest that the V162 allele of the human PPARA gene can be a new risk factor in the development of stage C heart failure, likely via depressed cardiac PPARα activity.
Teresa Arias; Javier Beaumont; Begoña López; Guillermo Zalba; Oscar Beloqui; Joaquín Barba; Félix Valencia; Juan José Gómez-Doblas; Eduardo De Teresa; Javier Díez
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  29     ISSN:  1473-5598     ISO Abbreviation:  J. Hypertens.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-08     Completed Date:  2011-07-29     Revised Date:  2011-08-31    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  876-83     Citation Subset:  IM    
Copyright Information:
© 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins
Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain.
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MeSH Terms
Acyl-CoA Dehydrogenase / genetics
Base Sequence
DNA Primers
Heart Failure / genetics*,  ultrasonography
Middle Aged
PPAR alpha / genetics*
Polymorphism, Genetic*
RNA, Messenger / genetics
Reg. No./Substance:
0/DNA Primers; 0/PPAR alpha; 0/RNA, Messenger; EC Dehydrogenase

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