title: Angiotensin I-converting enzyme gene polymorphism enhances the effect of hypercholesterolemia on the risk of coronary heart disease in a general Japanese population: the hisayama study.
abstract: OBJECTIVE
  The angiotensin I-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism has been reported to be implicated in susceptibility to coronary heart disease (CHD). However, this association remains inconclusive. The purpose of this study was to clarify the association between the I/D polymorphism of the ACE gene and the development of CHD in a Japanese general population and investigate whether the effects of traditional risk factors on the risk of CHD are heterogeneous among ACE genotypes.
  
  
  METHODS
  The subjects included 2,125 community-dwelling individuals 40 years of age or older without cardiovascular disease for whom genetic information was available. All patients were prospectively followed for 19 years, and the association between the ACE polymorphism and the incidence of CHD was examined based on the interactions with traditional risk factors, such as hypercholesterolemia, hypertension, diabetes and smoking.
  
  
  RESULTS
  A total of 161 CHD events occurred during the follow-up period. The age- and sex-adjusted incidence of CHD was not significantly different among the genotypes (5.8, 5.2, and 6.9 per 1,000person-years for genotypes II, ID and DD, respectively). In a stratified analysis, however, the ACE DD genotype was found to significantly accelerate the risk of developing CHD by hypercholesterolemia (hazard ratio [HR]=4.50, 95% confidence interval=2.02-10.04 for hypercholesterolemia with the DD genotype; HR=1.48, 95% CI=1.04-2.12 for hypercholesterolemia with the ID＋II genotype; P for interaction=0.01), even after adjusting for other confounding factors, whereas no such associations were observed for hypertension, diabetes or smoking.
  
  
  CONCLUSIONS
  The current findings suggest that the ACE DD genotype enhances the effect of hypercholesterolemia on the development of CHD in the general Japanese population.
authors.affiliation: Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kondo
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ninomiya
authors.forename: Jun
authors.initials: J
authors.lastname: Hata
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hirakawa
authors.forename: Koji
authors.initials: K
authors.lastname: Yonemoto
authors.forename: Hisatomi
authors.initials: H
authors.lastname: Arima
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nagata
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Tsuruya
authors.forename: Takanari
authors.initials: T
authors.lastname: Kitazono
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kiyohara
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000209:etiology*; D004198:Disease Susceptibility; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000235:genetics*; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A