European Journal of Epidemiology

, Volume 21, Issue 12, pp 859–867

A direct assessment of genetic contribution to the incidence of coronary infarct in the general population Greek EPIC cohort

  • Nikos Yiannakouris
  • Antonia Trichopoulou
  • Vassiliki Benetou
  • Theodora Psaltopoulou
  • Jose M. Ordovas
  • Dimitrios Trichopoulos
Cardiovascular Diseases

DOI: 10.1007/s10654-006-9070-5

Cite this article as:
Yiannakouris, N., Trichopoulou, A., Benetou, V. et al. Eur J Epidemiol (2006) 21: 859. doi:10.1007/s10654-006-9070-5

Abstract

To estimate the fraction of the incidence of coronary infarct attributable to the combined action of common genetic polymorphisms likely to be related to this condition, we conducted a case–control study nested within the Greek component of the European Prospective Investigation into Cancer and Nutrition. A total of 202 cases with a new, medically confirmed coronary infarct and 197 controls who had not developed an infarct by the time the corresponding case was diagnosed, were identified. A simple a priori score, relying on a total of 11 genetic polymorphisms was developed. Each polymorphism contributed 1 unit if the subject was homozygous for the high-risk allele, 0.5 units if the subject was heterozygous and 0 units if the subject was homozygous for the low-risk allele. Cases were over-represented in the presumed high genetic risk score values (chi square for trend = 10.18; p = 0.0014). The odds ratio to develop coronary infarct was 1.55 (95% confidence interval: 1.02–2.37) for score ≥3.0, and 2.02 (1.31–3.11) for score ≥3.5. In both instances the population fraction of the disease attributable to genetic predisposition exceeded 22%. Assuming a prior probability of at least 0.10 for the score to be predictive of coronary infarct risk, our findings are more likely than not to be truly positive. Our results, based on a simple score integrating the additive impact of 11 genetic polymorphisms, indicate that genetic predisposition accounts for a considerable fraction of the incidence of coronary infarct in the community.

Keywords

Coronary heart diseaseCoronary infarctGenetic predispositionPolymorphismsScore

Abbreviations

APO

Apolipoprotein

CHD

Coronary heart disease

NOS

Endothelial nitric oxide synthase

EPIC

European Prospective Investigation into Cancer and Nutrition

FPRP

False positive report probability

GPS

Genetic predisposition scale

Hcy

Homocysteine

IL

Interleukin

LD

Linkage disequilibrium

LPL

Lipoprotein lipase

MTHFR

Methylenetetrahydrofolate reductase

NO

Nitric oxide

TNF

Tumor necrosis factor

Copyright information

© Springer Science+Business Media B.V. 2006

Authors and Affiliations

  • Nikos Yiannakouris
    • 1
  • Antonia Trichopoulou
    • 2
  • Vassiliki Benetou
    • 2
  • Theodora Psaltopoulou
    • 2
  • Jose M. Ordovas
    • 3
  • Dimitrios Trichopoulos
    • 4
  1. 1.Harokopio University of AthensAthensGreece
  2. 2.Department of Hygiene and EpidemiologyUniversity of Athens Medical SchoolAthensGreece
  3. 3.Nutrition and Genomics Laboratory, Jean Mayer – US Department of AgricultureHuman Nutrition Research Center on Aging (HNRCA) at Tufts UniversityBostonUSA
  4. 4.Department of EpidemiologyHarvard School of Public HealthBostonUSA