Skip to main content
ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #218979
Title: Genetic predisposition, non-genetic risk factors and coronary infarct

Author
item Ordovas, Jose
item TRICHOPOULOU, ANTONIA - UNIV OF ATHENS, GREECE
item YIANNAKOURIS, NIKOS - HAROKOPIO UNIV, GREECE
item BAMIA, CHRISTINA - UNIV OF ATHENS, GREECE
item BENETOU, VASSILIKI - UNIV OF ATHENS, GREECE
item TRICHOPOULOS, DIMITRIOS - HARVARD SCHO OF PUB HEAL

Submitted to: Archives of Internal Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/13/2007
Publication Date: 4/28/2008
Citation: Ordovas, J.M., Trichopoulou, A., Yiannakouris, N., Bamia, C., Benetou, V., Trichopoulos, D. 2008. Genetic predisposition, non-genetic risk factors and coronary infarct. Archives of Internal Medicine. 168(8)891-896.

Interpretive Summary: Most common ailments affecting healthy aging in the general population are the result of complex interactions between genetic and environmental factors. Coronary heart disease (CHD) is the most common of those disorders in the US population and our current knowledge supports the notion that it is 50% driven by genetic factors and 50% driven by non-genetic factors, being dietary behaviour among the most important of the later. In terms of genes, many genes have been already implicated in the risk of CHD; however, the impact of each one of them is very small. Therefore, we have developed a genetic predisposition score (GPS), additively integrating the associations of 11 polymorphisms with coronary heart disease (CHD) and we examined the consequences of joint presence of high GPS and non-genetic CHD risk factors. For this purpose, we have used the Greek component of the European Prospective Investigation into Cancer (EPIC) and nutrition. Our data show that the joint presence of high GPS and each studied CHD risk factor (i.e., ever smoking, hypertension, low HDL-C, high non-HDL-C and poor adherence to Mediterranean diet) was in all instances associated with significantly increased risk of coronary infarction. Therefore, our study shows that genetic predisposition needs to interact with other risk factors (i.e., a poor diet) in the causation of CHD. Genetic predisposition and the other studied exposures appear to have converging effects. Therefore, the GPS may help on the identification of individuals who could gain disproportional benefits by controlling their blood pressure and adopting healthy dietary patterns.

Technical 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 joint presence of high GPS and non-genetic CHD risk factors. Methods: Within the European Prospective Investigation into Cancer and nutrition, 202 cases with medically confirmed incident coronary infarct and 197 controls were identified in Greece. Each polymorphism contributed in the GPS 1 unit (high-risk homozygous), 0.5 units (heterozygous) or 0 units (low-risk homozygous). Odds ratios (OR) of coronary infarction, for those at high risk because of genetic predisposition and simultaneous presence of an established CHD risk factor, were estimated versus subjects at low risk with respect to both GPS and each CHD risk factor. Results: Joint presence of high GPS (>3.5) and each studied CHD risk factor was in all instances associated with significantly increased risk of coronary infarction. The respective ORs (95% CI) were: 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 HDL, 3.05 (1.53-6.08) for high non-HDL and 3.66 (1.75-7.65) for poor adherence to Mediterranean diet. The ORs were always lower and non-significant when GPS was low. There was suggestive evidence for interaction of high GPS with hypertension (p=0.052) and non-HDL cholesterol (p=0.131). Conclusion: Genetic predisposition may interact with hypertension, and perhaps non-HDL cholesterol, in the causation of CHD. Genetic predisposition and the other studied exposures appear to have converging effects. Thus, GPS may identify individuals who could harvest disproportional benefits by controlling their blood pressure and, possibly, non-HDL cholesterol.