title: Genetic predisposition, nongenetic risk factors, and coronary infarct.
abstract: BACKGROUND
  Using a genetic predisposition score (GPS), additively integrating the associations of 11 polymorphisms with coronary heart disease (CHD), we examined the consequences of the joint presence of a high GPS and nongenetic CHD risk factors.
  
  
  METHODS
  Within the European Prospective Investigation Into Cancer and Nutrition, 202 case patients with medically confirmed incident coronary infarct and 197 control subjects were identified in Greece. Each polymorphism contributed 1 unit (high-risk homozygous), one-half unit (heterozygous), or no units (low-risk homozygous) to the GPS. Odds ratios of coronary infarction for those at high risk because of genetic predisposition and simultaneous presence of an established CHD risk factor were estimated, compared with subjects at low risk, for both GPS and each CHD risk factor.
  
  
  RESULTS
  The joint presence of a high GPS (> or =3.5) and each studied CHD risk factor was in all instances associated with a significantly increased risk of coronary infarction. The odds ratio (95% confidence interval) was 2.62 (1.14-6.02) for ever smoking, 2.88 (1.33-6.24) for hypertension, 3.50 (1.67-7.33) for low high-density lipoprotein (HDL) level, 3.05 (1.53-6.08) for high non-HDL level, and 3.66 (1.75-7.65) for poor adherence to the Mediterranean diet. The odds ratios were always lower and nonsignificant when the GPS was low. There was suggestive evidence for interaction of a high GPS with hypertension (P = .05) and non-HDL cholesterol level (P = .13).
  
  
  CONCLUSIONS
  Genetic predisposition may interact with hypertension and, perhaps, also with the level of non-HDL cholesterol, in the causation of CHD. Genetic predisposition and the other studied exposures seem to have converging effects. Thus, the GPS may identify individuals who could realize disproportional benefits by controlling their hypertension and, possibly, their non-HDL cholesterol level.
authors.affiliation: Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece.
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Nikos
authors.initials: N
authors.lastname: Yiannakouris
authors.forename: Christina
authors.initials: C
authors.lastname: Bamia
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Benetou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
mesh_terms: D016022:Case-Control Studies; D038441:Diet, Mediterranean; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006115:Greece / Q000453:epidemiology; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D016312:Treatment Refusal
chemical_list: D008075:Lipoproteins, HDL