title: PPARα gene polymorphisms modulate the association between physical activity and cardiometabolic risk.
abstract: OBJECTIVE
  Habitual physical activity is understood to help prevent type 2 diabetes and atherosclerotic cardiovascular disease via beneficial effects on both metabolism and the vascular system. However, individuals do not have uniform cardiometabolic responses to physical activity. Here we explore the extent to which variation in the proliferator-activated receptor-alpha (PPARα) gene, which modulates carbohydrate and lipid metabolism, vascular function, and inflammation, predicts the overall cardiometabolic risk (CMR) profile of individuals engaging in various levels of physical activity.
  
  
  RESULTS
  917 unrelated, community volunteers (52% female, of Non-Hispanic European ancestry) aged 30-54 years, participated in the cross-sectional study. Subjects were genotyped for 5 single nucleotide polymorphisms in the PPARα gene, from which common haplotypes were defined. A continuous measure of CMR was calculated as an aggregate of 5 traditional risk factors: waist circumference, resting blood pressure, fasting serum triglycerides, HDL-cholesterol and glucose. Regression models were used to examine the main and interactive effects of physical activity and genetic variation on CMR. One common PPARα haplotype (H-23) was associated with a higher CMR. This association was moderated by daily physical activity (B = -0.11, SE = 0.053, t = -2.05, P = 0.04). Increased physical activity was associated with a steeper reduction of CMR in persons carrying the otherwise detrimental H-23 haplotype.
  
  
  CONCLUSIONS
  Variations in the PPARα gene appear to magnify the cardiometabolic benefits of habitual physical activity.
authors.affiliation: Heart and Vascular Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: halderi@upmc.edu.
authors.forename: I
authors.initials: I
authors.lastname: Halder
authors.affiliation: Heart and Vascular Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: J
authors.initials: J
authors.lastname: Champlin
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Sheu
authors.affiliation: Heart and Vascular Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Goodpaster
authors.affiliation: Department of Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Manuck
authors.affiliation: Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Ferrell
authors.affiliation: Heart and Vascular Institute, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Muldoon
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D047493:PPAR alpha / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D055105:Waist Circumference
chemical_list: D047493:PPAR alpha
keywords: Cardiometabolic risk; Gene-by-physical activity interaction; Metabolic syndrome; Physical activity