The Role of Scavenger Receptor Class B Type 1 in Humans

B 型清道夫受体 1 在人类中的作用

• 批准号: 7983748
• 负责人: Annabelle Rodriguez
• 金额: $ 80.79万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7983748
• 关键词: Actins; Acylation; Adrenal Glands; Affect; African American; Alleles; Asians; Atherosclerosis; Biological Assay; Blood; Blood specimen; Body mass index; Cardiovascular Diseases; Cardiovascular system; Caucasians; Caucasoid Race; Cell membrane; Cells; Chemicals; Cholesterol; Cholesterol Esters; Code; DNA; Data; Docking; Endothelial Cells; Event; Female; Genes; Genetic; Genetic Polymorphism; Genetic Transcription; Genetic Variation; Genomics; Genotype; Goals; Haplotypes; Heart Diseases; Hepatocyte; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Hispanics; Human; Hydroxyl Radical; In Vitro; Infertility; Knockout Mice; Lipids; Lipoprotein Receptor; Lipoproteins; Measurement; Measures; Mediating; Messenger RNA; Minor; Mus; Myocardial Infarction; Outcome; Ovary; Participant; Particle Size; Persons; Plasma; Plasmids; Population; Primer Extension; Protein Deficiency; Proteins; RNA; Radiolabeled; Recruitment Activity; Regression Analysis; Research Project Grants; Risk; Role; SR-B proteins; SR-BI receptor; Sample Size; Sampling; Shapes; Specific qualifier value; Structure; Testing; Testis; Tissues; Translations; Variant; Very low density lipoprotein; Western Blotting; base; cardiovascular disorder risk; cohort; genetic association; high density lipoprotein receptor; inflammatory marker; insight; interest; macrophage; macrophage scavenger receptors; monocyte; premature; promoter; protein expression; public health relevance; radiotracer; receptor expression; research study; translation assay; uptake

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.

描述（由申请人提供）：高密度脂蛋白胆固醇（HDL-C）水平被认为可以预防心血管疾病。对于某些人群来说，这可能是真的，也可能不是。该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）的缺陷是否是导致高 HDL-C 水平的原因，并且可能是矛盾的是，导致心血管疾病风险增加。在具体目标 1 中，我们将进行体外实验来检查某些 SR-BI 基因 (SCARB1) 变体影响 SR-BI 蛋白表达的机制。在具体目标 2 中，我们将继续招募 HDL-C 水平高于 60 mg/dl 的受试者（这是因为水平高于 60 mg/dl 被认为具有心脏保护作用），并获取血液样本来测量胆固醇水平、DNA 和表达 SR-BI 蛋白的单核细胞来源的巨噬细胞。我们将检查 SCARB1 基因内的遗传变异与脂质水平、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 HDL 中摄取胆固醇酯来测量）的关联。我们还将检查动脉粥样硬化多种族研究 (MESA) 参与者和早发性心肌梗死受试者（心肌梗死遗传学联盟研究）的 SCARB1 多态性与血脂水平和亚临床动脉粥样硬化的关联。我们的研究结果将进一步深入了解 SR-BI 对 HDL-C 水平升高的受试者、以白种人、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) 以及早发心肌梗死受试者的血脂水平和心血管疾病的作用。 公共健康相关性：高密度脂蛋白 (HDL) 被认为是血液胆固醇水平的“健康”或“良好”部分。然而，尽管一个人的高密度脂蛋白水平达到理想水平，心脏病还是可能发生。我们的研究将检验 HDL 受体、B 类清道夫受体 I 型或 SR-BI 基因的变异是否可能与高 HDL 水平和心脏病相关。