title: The PPAR alpha gene is associated with triglyceride, low-density cholesterol and inflammation marker response to fenofibrate intervention: the GOLDN study.
abstract: As a peroxisome proliferator-activated receptor alpha (PPARα) agonist, fenofibrate favorably modulates dyslipidemia and inflammation markers, which are associated with cardiovascular risk. To determine whether variation in the PPARα receptor gene was associated with lipid and inflammatory marker response, we conducted a 3-week trial of fenofibrate in 861 men and women. Mixed linear models that controlled for age and sex, as well as family pedigree and study center, were constructed using single-nucleotide polymorphisms (SNPs) in the PPARα gene as predictors and changes in fasting triglycerides (TGs), cholesterol and inflammatory markers as outcomes. Significant associations with low-density cholesterol and interleukin-2 (P<0.001) responses to fenofibrate were found. Although there were suggestive associations with tumor necrosis factor-alpha and TG responses (P<0.05), these did not survive the correction for multiple testing. We conclude that variants in the PPARα gene may contribute to future pharmacogenomic paradigms seeking to predict fenofibrate responders from both an anti-dyslipidemic and anti-inflammatory perspective.
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. LekkiWood@Gmail.com
authors.forename: A C
authors.initials: AC
authors.lastname: Frazier-Wood
authors.forename: J M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: R J
authors.initials: RJ
authors.lastname: Straka
authors.forename: J E
authors.initials: JE
authors.lastname: Hixson
authors.forename: I B
authors.initials: IB
authors.lastname: Borecki
authors.forename: H K
authors.initials: HK
authors.lastname: Tiwari
authors.forename: D K
authors.initials: DK
authors.lastname: Arnett
mesh_terms: D000328:Adult; D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics*; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage*; D056726:Genetic Association Studies; D006801:Humans; D008055:Lipids / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D047493:PPAR alpha / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D008078:Cholesterol, LDL; D008055:Lipids; D047493:PPAR alpha; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D011345:Fenofibrate