期刊
JOURNAL OF HYPERTENSION
卷 29, 期 5, 页码 876-883出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0b013e3283455027
关键词
heart failure; polymorphism; PPAR alpha
资金
- Foundation for Applied Medical Research (FIMA)
- UTE project CIMA
- Instituto de Salud Carlos III
- Ministry of Health, Spain [RD06/0014/0008]
- European Union [LSHM-CT-2006-037093]
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) a 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 PPAR alpha 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 PPAR alpha activity. J Hypertens 29: 876-883 (C) 2011 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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