title: Peroxisome proliferator-activated receptor alpha gene variants influence progression of coronary atherosclerosis and risk of coronary artery disease.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptor alpha (PPARalpha) regulates the expression of genes involved in lipid metabolism and inflammation, making it a candidate gene for atherosclerosis and ischemic heart disease (IHD).
  
  
  RESULTS
  We investigated the association between the leucine 162 to valine (L162V) polymorphism and a G to C transversion in intron 7 of the PPARalpha gene and progression of atherosclerosis in the Lopid Coronary Angiography Trial (LOCAT), a trial examining the effect of gemfibrozil treatment on progression of atherosclerosis after bypass surgery and on risk of IHD in the second Northwick Park Heart Study (NPHS2), a prospective study of healthy middle-aged men in the United Kingdom. There was no association with plasma lipid concentrations in either study. Both polymorphisms influenced progression of atherosclerosis and risk of IHD. V162 allele carriers had less progression of diffuse atherosclerosis than did L162 allele homozygotes with a similar trend for focal atherosclerosis. Intron 7 C allele carriers had greater progression of atherosclerosis than did G allele homozygotes. The V162 allele attenuated the proatherosclerotic effect of the intron 7 C allele. Homozygotes for the intron 7 C allele had increased risk of IHD, an effect modulated by the L162V polymorphism
  
  
  CONCLUSIONS
  The PPARalpha gene affects progression of atherosclerosis and risk of IHD. Absence of association with plasma lipid concentrations suggests that PPARalpha affects atherosclerotic progression directly in the vessel wall.
authors.affiliation: Centre for Cardiovascular Genetics, Department of Medicine, Royal Free and University College of London Medical School, London, UK. d.flavell@ucl.ac.uk
authors.forename: David M
authors.initials: DM
authors.lastname: Flavell
authors.forename: Yalda
authors.initials: Y
authors.lastname: Jamshidi
authors.forename: Emma
authors.initials: E
authors.lastname: Hawe
authors.forename: Inés
authors.initials: I
authors.lastname: Pineda Torra
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: M Heikki
authors.initials: MH
authors.lastname: Frick
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Y Antero
authors.initials: YA
authors.lastname: Kesäniemi
authors.forename: Amos
authors.initials: A
authors.lastname: Pasternack
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.forename: George
authors.initials: G
authors.lastname: Miller
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Philippa J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: Mikko
authors.initials: M
authors.lastname: Syvänne
mesh_terms: D000368:Aged; D000483:Alleles; D019943:Amino Acid Substitution; D001161:Arteriosclerosis / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D015897:Comorbidity; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control; D018450:Disease Progression; D005387:Finland / Q000453:epidemiology; D015248:Gemfibrozil / Q000627:therapeutic use; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D007438:Introns; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D018570:Risk Assessment; D014157:Transcription Factors / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000960:Hypolipidemic Agents; D008055:Lipids; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D015248:Gemfibrozil