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

  • Cardiovascular Diseases
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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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Correspondence to Dimitrios Trichopoulos.

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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

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