title: Association and linkage disequilibrium analyses of APOE polymorphisms in atherosclerosis.
abstract: BACKGROUND
  Apolipoprotein E (apo E) plays a major role in lipid metabolism, and its genetic variations have been associated with cardiovascular risk. The objective of this study was to investigate the influence of the APOE promoter (-491 A/T, -427 T/C and -219 G/T) and coding region (APOE epsilon2/epsilon3/epsilon4) polymorphisms in atherosclerosis disease by association and linkage disequilibrium analyses.
  
  
  METHODS
  We analyzed these polymorphisms in a sample of 286 subjects with atherosclerosis disease: 153 subjects with atherothrombotic stroke (ATS) and 133 subjects with ischemic heart disease (IHD); and in two control groups, 103 newborns and 114 elderly subjects.
  
  
  RESULTS
  The epsilon4 allele was associated with more severe carotid stenosis in the ATS group, being the percentages of epsilon4 carriers 26.7% and 11.4% for the higher and lower carotid stenosis groups, respectively (p=0,066). The -491 T/T IHD subjects presented higher vessel scores than subjects A/A and A/T genotypes at that position (p=0,041), and the frequencies of -2 (5.1% versus 14.1%, p=0,060) and -427C (10.3% versus 24.4%, p=0,019) alleles were lower in IHD subjects with higher extent score versus lower extent score. The epsilon2 allele was in linkage disequilibrium with the -427C allele in all studied groups, and the -219T allele was associated with the epsilon4 allele in the IHD group.
  
  
  CONCLUSIONS
  In summary, the epsilon2 allele was in linkage disequilibrium with the -427C allele in all studied groups, and only slight associations between the analyzed APOE polymorphisms in the promoter and in the coding region and carotid and coronary vascular disease have been observed.
authors.affiliation: Laboratory of Molecular Investigation, University Hospital Miguel Servet, Aragonian Health Sciences Institute, Zaragoza, Spain. martieda@salud.aragon.es
authors.forename: Marta
authors.initials: M
authors.lastname: Artieda
authors.forename: Alberto
authors.initials: A
authors.lastname: Gañán
authors.forename: Ana
authors.initials: A
authors.lastname: Cenarro
authors.forename: Angel Luis
authors.initials: AL
authors.lastname: García-Otín
authors.forename: Ivonne
authors.initials: I
authors.lastname: Jericó
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
authors.forename: Miguel
authors.initials: M
authors.lastname: Pocoví
mesh_terms: D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D020521:Stroke / Q000235:genetics
chemical_list: D001057:Apolipoproteins E