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.
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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
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Acknowledgments
This study was supported by the Europe against Cancer Program of the European Commission, the Greek Ministries of Health and Education, and the Hellenic Health Foundation. Also supported by NIH/NHLBI Grant no. HL54776 and 58-1950-9-001 from the U.S. Department of Agriculture Research Service.
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Yiannakouris, N., Trichopoulou, A., Benetou, V. et al. A direct assessment of genetic contribution to the incidence of coronary infarct in the general population Greek EPIC cohort. Eur J Epidemiol 21, 859–867 (2006). https://doi.org/10.1007/s10654-006-9070-5
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DOI: https://doi.org/10.1007/s10654-006-9070-5