Publicações científicas

Association of the peroxisome proliferator-activated receptor α gene L162V polymorphism with stage C heart failure

Arias T, Beaumont J, López B, Zalba G, Beloqui O, Barba J [ES], Valencia F, Gómez-Doblas JJ, De Teresa E, Díez J.
Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain

Revisão:Journal of Hypertension

Data: 1/Mai/2011

Cardiología Unidade de Check-Up

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.

CITAÇÃO DO ARTIGO  J Hypertens. 2011 May;29(5):876-83

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