Genetic Factors and Cardiovascular Disease

描述 （申请人摘要）冠状动脉心脏病（CHD）是心脏病的主要原因。 在美国和发达国家。 中风和外周 血管疾病（PVD）在美国非常普遍， 高昂的医疗费用。对决定因素的了解有限 心血管疾病（CVD），以及缺乏遗传作用的细节， 基因-基因和基因-环境交互作用对 心血管疾病阻碍了预防这些疾病的努力。 适量饮酒与降低冠心病、心血管疾病的风险有关， 以及总体死亡率，部分原因是高密度脂蛋白胆固醇升高。 醇 脱氢酶（ADH）是血液中代谢酒精的酶。 而 医师健康研究表明ADH-3的效果改变 关于酒精摄入量与冠心病的关系，数据有限， ADH是否改变酒精摄入量与CVD危险因素之间的关系 还有CHD 关于ADH和频率之间的关系知之甚少， 酒精的种类和数量。 另一种常见的基因变异，刘易斯（a- B-）与CHD的高风险相关。 然而， 刘易斯（a-b-）对中风和PVD的研究还没有很好的建立， 研究这些遗传因素的潜在相互作用。 我们将使用收集到的关于Fragmentary Offspring参与者的数据来测试1） ADH 3基因型的变异是否改变了酒精与 摄入量和CHD、HDL-胆固醇、频率、量和酒精类型 刘易斯（a-b-）是否是CVD的独立危险因素; 3） 酒精摄入是否改变了刘易斯（a-b-）和CVD之间的关联; 刘易斯（a-b-）是否与PVD的高风险相关。 最后我们 将使用GENCAC研究参与者的数据来评估这些 与冠状动脉钙化有关的遗传因素， 动脉粥样硬化

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.