This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (4)  • Contact me when this article is cited  Related Content  • Similar articles in this journal  Topic Collections  • Lipids and Lipid Disorders  • Tobacco  • Cardiovascular System  • Diet  • Cardiovascular Disease/ Myocardial Infarction  • Genetics  • Genetic Disorders  • Hypertension  • Alert me on articles by topic  Social Bookmarking   What's this?

Arch Intern Med. 2008;168(8):891-896.

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 (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.

Author Affiliations: Department of Hygiene and Epidemiology, University of Athens Medical School (Drs Trichopoulou, Bamia, and Benetou), Harokopio University of Athens (Dr Yiannakouris), and Hellenic Health Foundation (Dr Trichopoulos), Athens, Greece; and Department of Epidemiology, Harvard School of Public Health (Dr Trichopoulos), and Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging, Tufts University (Dr Ordovas), Boston, Massachusetts.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states
Perez-Martinez et al.
Am. J. Clin. Nutr. 2009;89:391-399.
ABSTRACT | FULL TEXT