The Role of Scavenger Receptor Class B Type 1 in Humans

描述(申请人提供)：高密度脂蛋白胆固醇(高密度脂蛋白胆固醇)水平被认为可以预防心血管疾病。在某些人群中，这可能是真的，也可能不是。这项研究项目的长期目标是确定脂蛋白受体B型清道夫受体I型或SR-BI的缺陷是否是高密度脂蛋白水平的原因，或许矛盾的是，它增加了心血管疾病的风险。在具体目标1中，我们将进行体外实验，以探讨某些SR-BI基因(SCARB1)变异影响SR-BI蛋白表达的机制(S)。在具体目标2中，我们将继续招募高密度脂蛋白水平高于60 mg/dl的受试者(这是因为高于60 mg/dl被认为对心脏有保护作用)，并获取血液样本以测量胆固醇水平、DNA和表达SR-BI蛋白的单核细胞来源的巨噬细胞。我们将研究SCARB1基因内的遗传变异与血脂水平、巨噬细胞SR-BI蛋白和RNA表达以及SR-BI功能(通过从放射性标记的高密度脂蛋白中摄取胆固醇酯来衡量)之间的关系。我们还将在动脉粥样硬化多种族研究(MESA)的参与者和早产性心肌梗死患者(心肌梗死遗传学联合研究)的参与者中检查SCARB1基因多态与血脂水平和亚临床动脉粥样硬化的关系。我们的研究结果将进一步深入了解SR-BI在高密度脂蛋白-C水平升高的受试者、以高加索人、非裔美国人、西班牙裔和亚洲血统的人为代表的较大人群(MESA)以及早发性心肌梗塞受试者中对血脂水平和心血管疾病的作用。 与公众健康相关：高密度脂蛋白(高密度脂蛋白)被认为是血液胆固醇水平中“健康”或“良好”的部分。然而，尽管一个人的高密度脂蛋白水平令人满意，但心脏病仍有可能发生。我们的研究将检验高密度脂蛋白受体基因的变异是否可能与高密度脂蛋白水平和心脏病有关。

DESCRIPTION (provided by applicant): High density lipoprotein cholesterol (HDL-C) levels are thought to protect against cardiovascular disease. This may or may not be true in certain populations. The long-term goal of this research project is to determine if a deficiency in the lipoprotein receptor, scavenger receptor class B type I or SR-BI, is a cause of high levels of HDL-C and, perhaps paradoxically, an increased risk for cardiovascular disease. In specific aim 1, we will perform in vitro experiments to examine the mechanism(s) by which certain SR-BI gene (SCARB1) variants affect SR-BI protein expression. In specific aim 2, we will continue recruiting subjects with HDL-C levels above 60 mg/dl (this is because levels above 60 mg/dl are thought to be cardioprotective) and obtaining blood specimens to measure cholesterol levels, DNA, and monocyte-derived macrophage that express SR-BI protein. We will examine the association of genetic variations within the SCARB1 gene with lipid levels, macrophage SR-BI protein and RNA expression and SR-BI function (as measured by the uptake of cholesteryl esters from radiolabeled HDL). We will also examine the association of SCARB1 polymorphisms and lipid levels and subclinical atherosclerosis in participants of the Multi-Ethnic Study of Atherosclerosis (MESA) and in subjects with premature myocardial infarction (Myocardial Infarction Genetics Consortium Study). The results from our studies will provide further insight into the role of SR-BI on lipid levels and cardiovascular disease in subjects with elevated levels of HDL-C, in a larger population (MESA) well-represented by persons of Caucasian, African-American, Hispanic and Asian ancestry, and in subjects with premature myocardial infarction. PUBLIC HEALTH RELEVANCE: High density lipoproteins (HDL) are considered the "healthy" or "good" fraction of the blood cholesterol levels. However, heart disease can occur despite a person having desirable levels of HDL. Our study will examine whether variations in the gene for the HDL receptor, scavenger receptor class B type I or SR-BI, might be associated with good levels of HDL and heart disease.