THE PCSK9 GENE: RELATIONSHIP TO HUMAN HEALTH

PCSK9 基因：与人类健康的关系

• 批准号: 7606356
• 负责人: Helen Haskell Hobbs
• 金额: $ 0.01万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7606356
• 关键词: Affect; Alleles; Americas; Cause of Death; Cholesterol Homeostasis; Clinical Pathology; Computer Retrieval of Information on Scientific Projects Database; Coronary Arteriosclerosis; Ensure; Family; Family member; Funding; Genes; Genetic; Goals; Grant; Health; Human; Individual; Institution; LDL Cholesterol Lipoproteins; Low-Density Lipoproteins; Numbers; Organ; Physiological; Plasma; Play; Research; Research Personnel; Resources; Risk Factors; Role; Serine Protease; Source; Today; United States National Institutes of Health; Variant; diet and exercise; research clinical testing

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Circulating levels of LDL constitute the major risk factor for coronary artery disease--the largest cause of death in America today. Plasma levels of LDL-cholesterol vary from individual to individual. While 50% of this variation is attributable to diet, exercise and other factors, 50% of this variation is attributable to genetics. PCSK9 is a secreted serine protease that plays a critical role in cholesterol homeostasis. Select sequence variations in PCSK9 that result in low plasma LDL-cholesterol have been identified in family DHS20 (study #1287-355). So far, family members with no affected alleles, one affected allele and both affected alleles have been identified. While plasma level of LDL-cholesterol vary according to the number of affected alleles, no additional differences in physiologic parameters have been observed. To ensure that the absence of PCSK9 does not confer additional physiologic change beyond its effect on plasma LDL-cholesterol, we wish to perform a comprehensive clinical evaluation of subjects with absent, low and normal levels of plasma PCSK9. Ultimately the goal of the project is to determine if the absence of circulating PCSK9 is related to clinical pathology within and beyond the organs in which PCSK9 is expressed.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 循环中的低密度脂蛋白水平是冠状动脉疾病的主要危险因素，而冠状动脉疾病是当今美国最大的死亡原因。低密度脂蛋白胆固醇的血浆水平因人而异。虽然这种差异的 50% 可归因于饮食、锻炼和其他因素，但这种差异的 50% 可归因于遗传。 PCSK9 是一种分泌型丝氨酸蛋白酶，在胆固醇稳态中发挥着关键作用。 已在 DHS20 家族中鉴定出 PCSK9 中导致血浆低密度脂蛋白胆固醇降低的特定序列变异（研究#1287-355）。 到目前为止，已经确定了没有受影响等位基因、一个受影响等位基因和两个受影响等位基因的家庭成员。 虽然低密度脂蛋白胆固醇的血浆水平根据受影响的等位基因的数量而变化，但尚未观察到生理参数的额外差异。 为了确保 PCSK9 的缺失不会带来除了对血浆 LDL-胆固醇影响之外的额外生理变化，我们希望对血浆 PCSK9 缺失、低水平和正常水平的受试者进行全面的临床评估。该项目的最终目标是确定循环 PCSK9 的缺失是否与表达 PCSK9 的器官内外的临床病理有关。