APOLIPOPROTEIN POLYMORPHISMS AND RISK OF CHD

载脂蛋白多态性与冠心病风险

• 批准号: 3355255
• 负责人: RICHARD H WARD
• 金额: $ 19.65万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3355255
• 关键词: alleles; angiography; apolipoproteins; biological polymorphism; cardiovascular disorder diagnosis; cardiovascular disorder epidemiology; cholesterol; coronary disorder; density gradient ultracentrifugation; disease /disorder proneness /risk; electrofocusing; electrophoresis; genome; genotype; high density lipoproteins; human ecology; human subject; low density lipoprotein; statistics /biometry; triglycerides; very low density lipoprotein

Coronary Heart Disease (CHD) is a major cause of early death in the U.S. Numerous epidemiological studies have shown that the risk of CHD is strongly influenced by plasma lipid levels, especially HDL and LDL cholesterol, and their specific apolipoprotein constituents. Genetic studies have established significant heritability of these lipid components, and have also identified relatively rare major genes that result in extreme lipid values and increased risk of CHD. Recently, geneticist have identified a number of segregating polymorphisms at the four major apolipoprotein genomic regions, using a combination of protein and DNA assays. However, the relationship between these polymorphisms and risk of CHD has not yet been properly defined. This study aims to determine the relative risk of angiographically defined coronary artery disease (CAD) in a defined population (Washach Front and southern Idaho), due to genetic polymorphism at the four apolipoprotein genomic regions. We will use a case- control approach to identify the specific polymorphisms (both single sites, and haplotypes) that confer elevated risk of CAD, and determine whether these polymorphisms are associated with distinct lipid profiles, or interact with known environmental risk factors. This will be achieved by evaluating DNA polymorphisms, protein polymorphisms, lipid profiles, and epidemiological risk factors in 400 cases with angiographically defined disease, 400 age-sex matched controls with angiographically proven normal coronary arteris, and 400 age-sex matched controls with angiographically proven normal coronary arteris, and 400 age-sex matched random controls. Also, 800 first degree relatives will be typed for DNA polymorphisms, to define complex haplotypes for each of these genomic regions, as combinations of several segregating polymorphisms. The contribution of these four apolipoprotein genomic regions to risk of CAD will be estimated in a number of ways. First, the direct association of CAD risk with the presence of specific alleles, or genotypes, will be estimated be calculating odds ratios. Second, the influence of genetic segregation at these four apolipoprotein regions on lipid profiles will be estimated to evaluate the indirect influence of these loci on CAD risk. Third, interactions between the polymorphisms at these loci and specific environmental risk factors will be evaluated to determine to what extent risk of CAD is due to interaction between deleterious environments and susceptible genotypes.

冠心病（CHD）是导致人们过早死亡的主要原因 美国大量流行病学研究表明 冠心病的风险很大程度上受血浆脂质水平的影响， 尤其是 HDL 和 LDL 胆固醇，以及它们的具体 载脂蛋白成分。 遗传学研究已确定 这些脂质成分具有显着的遗传性，并且还具有 鉴定出相对罕见的导致极端脂质的主要基因 值和冠心病风险增加。 最近，遗传学家 发现了四个分离多态性 主要载脂蛋白基因组区域，使用组合 蛋白质和 DNA 测定。 然而，这些之间的关系 多态性和冠心病风险尚未得到正确定义。 本研究旨在确定血管造影的相对风险 特定人群中的特定冠状动脉疾病 (CAD) （瓦什赫前沿和爱达荷州南部），由于遗传多态性 在四个载脂蛋白基因组区域。 我们将使用一个案例—— 控制方法来识别特定的多态性（两者 单个位点和单倍型）会导致 CAD 风险升高，以及 确定这些多态性是否与 不同的脂质分布，或与已知的环境风险相互作用 因素。 这将通过评估 DNA 多态性来实现， 蛋白质多态性、血脂谱和流行病学风险 第 400 章 年龄-性别匹配的对照，血管造影证明正常 冠状动脉，以及 400 名年龄性别匹配的对照 血管造影证明冠状动脉正常，400 年龄性别 匹配的随机对照。 此外，800名一级亲属将 DNA 多态性分型，定义复杂的单倍型 这些基因组区域中的每一个，作为几个的组合 分离多态性。 这四个载脂蛋白基因组区域对 CAD 风险可通过多种方式进行评估。 首先， CAD 风险与特定疾病的存在直接相关 等位基因或基因型将通过计算优势比来估计。 其次，这四种基因分离的影响 脂质谱上的载脂蛋白区域将估计为 评估这些位点对 CAD 风险的间接影响。 第三， 这些位点的多态性与特定的多态性之间的相互作用 将评估环境风险因素，以确定哪些因素 CAD 风险的程度是由于有害物质之间的相互作用 环境和易感基因型。

项目成果

Apolipoprotein polymorphisms fail to define risk of coronary artery disease. Results of a prospective, angiographically controlled study.

载脂蛋白多态性无法定义冠状动脉疾病的风险。

• DOI: 10.1161/01.cir.89.2.567
• 发表时间: 1994
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Marshall,HW;Morrison,LC;Wu,LL;Anderson,JL;Corneli,PS;Stauffer,DM;Allen,A;Karagounis,LA;Ward,RH
• 通讯作者: Ward,RH