Genetic Factors and Cardiovascular Disease

描述 (申请人摘要)冠心病(CHD)是导致 美国和发达国家的死亡人数。中风和外周 血管疾病(PVD)在美国非常流行，与 高昂的医疗保健费用。对疾病决定因素的认识有限 心血管疾病(CVD)，以及缺乏关于基因的作用的细节 基因-基因和基因-环境相互作用的影响因素 心血管疾病，阻碍了旨在预防这些疾病的努力。 适度饮酒与患冠心病、心血管疾病的风险较低有关， 和总死亡率，部分原因是高密度脂蛋白胆固醇升高。酒精 脱氢酶(ADH)是血液中代谢酒精的酶。而当 医生的健康研究建议对ADH-3进行有效修改 饮酒与冠心病关系的多态，数据仅限于 ADH是否改变了饮酒与心血管疾病危险因素之间的关系 和先心病。ADH与频率之间的关系知之甚少， 饮酒量和饮酒类型。另一种常见的基因变异，Lewis(a- B-)与患冠心病的风险较高有关。然而，它的影响 Lewis(a-b-)对卒中和PVD的作用还没有很好的确立，也没有 对这些遗传因素潜在相互作用的研究。 我们将使用收集的关于Framingham子孙参与者的数据来测试1) ADH3基因变异是否改变了酒精与酒精之间的联系 摄入量与CHD、高密度脂蛋白-胆固醇、饮酒频率、饮酒量和饮酒类型 2)Lewis(a-b-)是否是心血管疾病的独立危险因素；3) 酒精摄入是否改变了Lewis(a-b-)与心血管疾病之间的联系； 以及40 Lewis(a-b-)是否与PVD的高风险相关。最后，我们 将使用收集的关于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，这是一种衡量冠状动脉的指标 动脉硬化。

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.