APOLIPOPROTEIN POLYMORPHISMS AND RISK OF CHD
APOLIPOPROTEIN POLYMORPHISMS AND RISK OF CHD
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
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
中文摘要
冠心病(CHD)是老年人早期死亡的主要原因。
许多流行病学研究表明,
CHD的风险受到血浆脂质水平的强烈影响,
尤其是HDL和LDL胆固醇,
载脂蛋白组分。 遗传学研究已经建立了
这些脂质成分的显著遗传性,
确定了相对罕见的导致极端脂质的主要基因,
增加CHD的风险。 最近,遗传学家
发现了一些分离的多态性,在四个
主要载脂蛋白基因组区域,使用以下组合
蛋白质和DNA分析。 然而,这些之间的关系
多态性和CHD的风险尚未得到适当的定义。
本研究的目的是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)
(瓦萨赫前线和爱达荷州南部),由于遗传多态性
在四个载脂蛋白基因组区域。 我们会用一个案例-
控制方法,以确定特定的多态性(两者
单一位点和单倍型),这些位点和单倍型会增加CAD的风险,以及
确定这些多态性是否与
不同的脂质特征,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
在400例血管造影定义的疾病中,
血管造影证实正常的年龄-性别匹配对照
冠状动脉,和400名年龄性别匹配的对照组,
冠状动脉造影证实正常,400名年龄-性别
匹配随机对照。 此外,800名一级亲属将被
DNA多态性,以确定复杂的单倍型,
这些基因组区域中的每一个,作为几个
分离多态性。
这四个载脂蛋白基因组区域对
CAD的风险将以多种方式进行评估。 一是
CAD风险与存在特定
等位基因或基因型将通过计算优势比来估计。
二是遗传分离对这四个方面的影响
载脂蛋白区域对血脂谱的影响将被估计为
评估这些位点对CAD风险的间接影响。 第三、
这些基因座的多态性与特异性
将评估环境风险因素,以确定
CAD的风险程度是由于有害物质之间的相互作用
环境和易感基因型。
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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批准号:3300109
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依托单位:
APOLIPOPROTEIN POLYMORPHISMS AND RISK OF CHD
-
批准号:3355255
-
项目类别:
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资助金额:$19.65万
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负责人:RICHARD H WARD
-
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APOLIPOPROTEIN POLYMORPHISMS AND RISK OF CHD
-
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项目类别:
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GENETIC EPIDEMIOLOGY OF HUMAN FETAL GROWTH
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