ArticlePharmacogenomics2008
Interaction between PPARA genotype and beta-blocker treatment influences clinical outcomes following acute coronary syndromes.
Article in Pharmacogenomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
9 citing papers in PubMed, 19 citations in OpenAlex.
- Prognostic and functional role of PPAR-alpha and SNP receptor (Leu162Val) in acute coronary syndrome: a potential novel target.Journal, genetic engineering & biotechnology · 2025Article
- Association of plasma metabolites and cardiac mitochondrial function with heart failure progression.ESC heart failure · 2025Article
- Does theJournal of human kinetics · 2021Article
- The Polymorphisms of the Peroxisome-Proliferator Activated Receptors' Alfa Gene Modify the Aerobic Training Induced Changes of Cholesterol and Glucose.Journal of clinical medicine · 2019Article
- Association between the EPHX2 p.Lys55Arg polymorphism and prognosis following an acute coronary syndrome.Prostaglandins & other lipid mediators · 2018Article
- PPARα gene polymorphisms modulate the association between physical activity and cardiometabolic risk.Nutrition, metabolism, and cardiovascular diseases : NMCD · 2014Article
- PPARA intron polymorphism associated with power performance in 30-s anaerobic Wingate Test.PloS one · 2014Article
- Disease registries and outcomes research in children: focus on lysosomal storage disorders.Paediatric drugs · 2011Review
- PPAR transcriptional activator complex polymorphisms and the promise of individualized therapy for heart failure.Heart failure reviews · 2010Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
aimsbeta-blockers (BB) are strongly recommended after an acute coronary syndrome (ACS), although all patients may not benefit. Causes for variable patient responses to BB are unknown. Given that myocardial ischemia and BB influence metabolic processes regulated by peroxisome proliferator-activated receptor alpha (PPARalpha), we hypothesized that interactions between polymorphisms of the PPARalpha gene (PPARA) and BB treatment would influence clinical outcome following ACS. PATIENTS &
methodsPatients were prospectively enrolled into an ACS registry. A total of 735 ACS patients were genotyped. Mortality and cardiac rehospitalization through 1 year were analyzed in relation to PPARA genotype and BB prescription (597 BB; 138 no BB) at discharge.
resultsSignificantly different outcomes associated with BB therapy were observed according to PPARA IVS7 2498 genotype (p = 0.002 for interaction). PPARA IVS7 2498 GG homozygous patients discharged on BB had decreased cardiac rehospitalization (hazard ratio [HR]: 0.52; 95% CI: 0.32-0.86; p = 0.011), while C allele carriers discharged on BB had nearly threefold increased cardiac rehospitalization (HR: 2.92; 95% CI: 1.32-6.92; p = 0.015; genotype interaction p = 0.0005) compared with patients not on BB. PPARA genotype was also associated with differences in PPARalpha expression, with significantly increased mRNA levels in myocardial samples from normal hearts among GC heterozygotes compared with GG homozygotes (p = 0.04). Transgenic mice with cardiac-specific overexpression of PPARalpha showed significantly reduced myocardial contractile and chronotropic responses to the beta-sympathomimetic dobutamine (p < 0.05) compared with wild-type littermates, supporting the hypothesis that increased PPARalpha levels result in a blunted beta-adrenergic response.
conclusionsPPARA IVS7 2498 genotype is associated with heterogeneity in 1-year outcome in response to BB among patients following ACS, and may predict which patients benefit from BB therapy, putatively related to the effect of myocardial PPARalpha expression on beta-adrenergic responsiveness.
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