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APOLIPOPROTEIN POLYMORPHISMS AND RISK OF CHD

APOLIPOPROTEIN POLYMORPHISMS AND RISK OF CHD
载脂蛋白多态性与冠心病风险
批准号:
3355253
负责人:
RICHARD H WARD
金额:
$25.9万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1988
资助国家:
美国
项目状态:
已结题
起止时间:
1988-04-01 至 1991-03-31

项目摘要

项目成果

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中文摘要
翻译
冠心病(CHD)是#年导致过早死亡的主要原因。 美国众多的流行病学研究表明, 患冠心病的风险受血脂水平的影响很大, 尤其是高密度脂蛋白和低密度脂蛋白,以及它们的特异性 载脂蛋白成分。基因研究已经建立了 这些脂质成分的显著遗传力,也有 发现了相对罕见的导致极端脂肪的主效基因 冠心病的价值和增加的风险。最近,遗传学家已经 在这四个基因中发现了一些分离多态 主要载脂蛋白基因组区域,使用 蛋白质和DNA检测。然而,这两者之间的关系 基因多态与冠心病发病风险的关系尚未得到正确的定义。 这项研究旨在通过血管造影术来确定 限定人群中的限定冠状动脉疾病(CAD) (沃萨奇前线和爱达荷州南部),由于基因多态 在载脂蛋白基因组的四个区域。我们将用一个案例- 对照方法来识别特定的多态(两者 单一位点和单倍型)会增加患冠心病的风险,以及 确定这些多态是否与 不同的血脂特征,或与已知的环境风险相互作用 各种因素。这将通过评估DNA多态来实现, 蛋白质多态、脂谱与流行病学风险 400例血管造影明确疾病患者的相关因素 年龄-性别匹配的对照组,血管造影证实正常 冠状动脉病变,以及400名年龄-性别匹配的对照组 冠状动脉造影术证实冠状动脉正常,400名年龄-性别 与随机对照相匹配。此外,800名一级亲属将成为 DNA多态类型,以定义复杂的单倍型 这些基因组区域中的每一个,作为几个 分离的多态。 这四个载脂蛋白基因组区域对载脂蛋白的贡献 CAD的风险将通过多种方法进行评估。首先, 冠心病风险与特定疾病的存在直接相关 等位基因或基因类型将通过计算优势比来估计。 第二,遗传分离对这四个国家的影响 脂蛋白谱上的载脂蛋白区域将估计为 评估这些基因座对冠心病风险的间接影响。第三, 这些基因座上的多态与特定基因座的交互作用 将对环境风险因素进行评估,以确定 冠心病的程度风险是由于有害因素之间的相互作用 环境和易感基因类型。
英文摘要
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.
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DNA POLYMORPHISMS IN NORTH AMERICAN INDIANS
  • 批准号:
    3300109
  • 项目类别:
  • 资助金额:
    $17.67万
  • 财政年份:
    1989
  • 负责人:
    RICHARD H WARD
  • 依托单位:
DNA POLYMORPHISMS IN NORTHERN NATIVE AMERICANS
  • 批准号:
    2181029
  • 项目类别:
  • 资助金额:
    $24.38万
  • 财政年份:
    1989
  • 负责人:
    RICHARD H WARD
  • 依托单位:
DNA POLYMORPHISMS IN NORTH AMERICAN INDIANS
  • 批准号:
    3300114
  • 项目类别:
  • 资助金额:
    $17.43万
  • 财政年份:
    1989
  • 负责人:
    RICHARD H WARD
  • 依托单位:
DNA POLYMORPHISMS IN NORTH AMERICAN INDIANS
  • 批准号:
    3300113
  • 项目类别:
  • 资助金额:
    $17.37万
  • 财政年份:
    1989
  • 负责人:
    RICHARD H WARD
  • 依托单位:
海外基金