title: Age-dependent interaction of apolipoprotein E gene with eastern birthplace in Finland affects severity of coronary atherosclerosis and risk of fatal myocardial infarction--Helsinki Sudden Death Study.
abstract: BACKGROUND
  Mortality from coronary heart disease (CHD) has been constantly higher in eastern late settlement regions compared to western early settlements in Finland, unrelated to classical risk factors. In line with this, eastern birthplace was an age-dependent predictor of severe coronary atherosclerosis and pre-hospital sudden coronary death among male residents of Helsinki. We investigated a possible interaction of apolipoprotein E (APOE) gene with birthplace on the risk of myocardial infarction (MI) and coronary atherosclerosis.
  
  
  METHODS
  APOE genotypes were analyzed in the Helsinki Sudden Death Study series comprising out-of-hospital deaths among males aged 33-70 years (n = 577), who were born in high (east, n = 273) or low (west, n = 304) CHD mortality area.
  
  
  RESULTS
  Eastern-born men ≤ 55 years carried 30% more often (P = 0.017) and older men 40% less often (P = 0.022) the APOE ϵ4 allele compared to western-born men (P = 0.003 for birthplace-by-age interaction). In multivariate analysis, the ϵ4 allele associated with the risk of out-of-hospital MI (odds ratio 2.58; 95% CI 1.20-5.55; P = 0.016) only in eastern-born men and with advanced atherosclerosis in both regions of origin, respectively.
  
  
  CONCLUSIONS
  Birthplace-bound risk of CHD was age-dependently modified by APOE ϵ4 allele, suggesting genetic differences in CHD susceptibility between early and late settlement regions in Finland and providing one explanation for the eastern high mortality.
authors.affiliation: School of Medicine, University of Tampere, Tampere, Finland. petri.tyynela@uta.fi
authors.forename: Petri
authors.initials: P
authors.lastname: Tyynelä
authors.forename: Sirkka
authors.initials: S
authors.lastname: Goebeler
authors.forename: Erkki
authors.initials: E
authors.lastname: Ilveskoski
authors.forename: Jussi
authors.initials: J
authors.lastname: Mikkelsson
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Pekka J
authors.initials: PJ
authors.lastname: Karhunen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics*; D003324:Coronary Artery Disease / Q000401:mortality*; D003331:Coronary Vessels / Q000473:pathology; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D005387:Finland / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D058687:Out-of-Hospital Cardiac Arrest / Q000401:mortality*; D058226:Plaque, Atherosclerotic / Q000473:pathology; D012111:Residence Characteristics; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D001057:Apolipoproteins E