Genetic Factors and Cardiovascular Disease

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DESCRIPTION (Applicant's abstract) Coronary heart disease (CHD) is the leading cause of death in the United States and in developed countries. Stroke and peripheral vascular disease (PVD) are highly prevalent in the US and are associated with a high health care cost. Limited knowledge on the determinants of cardiovascular disease (CVD), and the lack of details on the role of genetic factors and the influence of gene-gene and gene-environmental interactions on CVD, have hampered efforts directed at preventing those diseases. Moderate alcohol consumption has been associated with lower risk of CHD, CVD, and overall mortality, partially through elevated HDL cholesterol. Alcohol dehydrogenase (ADH) is the enzyme that metabolizes alcohol in blood. While the Physician's Health Study suggested an effect modification of ADH-3 polymorphism on the relation of alcohol intake to CHD, data are limited on whether ADH modifies the relation between alcohol intake and CVD risk factors and CHD. Little is known about the relation between ADH and the frequency, amount, and type of alcohol consumed. Another common gene variant, Lewis (a- b-) has been associated with higher risk of CHD. However, the effects of Lewis (a-b-) on stroke and PVD are not well established, and there are no studies of potential interaction of these genetic factors. We will use data collected on Framingham Offspring participants to test 1) whether variants of ADH3 genotypes modify the association between alcohol intake and CHD, HDL-cholesterol, frequency, amount, and type of alcohol consumed; 2) whether Lewis (a-b-) is an independent risk factor of CVD; 3) whether alcohol intake modifies the association between Lewis (a-b-) and CVD; and 40 whether Lewis (a-b-) is associated with higher risk of PVD. Lastly, we will use data collected on participants of the GENCAC study to evaluate these genetic factors in relation to coronary calcification, a measure of coronary atherosclerosis.