STUDIES IN CARDIOVASCULAR DISEASE

心血管疾病研究

• 批准号: 8171734
• 负责人: Robert C. Elston
• 金额: $ 0.49万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171734
• 关键词: 15q22; 15q25; 7p22; Accounting; Age; Cardiovascular Diseases; Chromosomes; Computer Retrieval of Information on Scientific Projects Database; Coronary Arteriosclerosis; Family; Funding; Gender; Genes; Genetic Variation; Grant; Heritability; High Density Lipoprotein Cholesterol; Institution; Maps; Metabolism; Minor; Plasma; Population; Quantitative Trait Loci; Research; Research Personnel; Resources; Scanning; Source; Testing; United States National Institutes of Health; Variant; base; cohort; genome-wide linkage; insight; novel; premature; transmission process

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. Plasma HDL cholesterol levels (HDL-C) are an independent predictor of coronary artery disease (CAD). We have completed a genome-wide linkage scan for HDL-C in a US cohort consisting of 388 multiplex families with premature CAD (GeneQuest). The heritability of HDL-C in GeneQuest was 0.37 with gender and age as covariates (P = 5.1 x 10(-4)). Two major quantitative trait loci (QTL) for log-transformed HDL-C adjusted for age and gender were identified onto chromosomes 7p22 and 15q25 with maximum multipoint logarithm of odds (LOD) scores of 3.76 and 6.69, respectively. Fine mapping decreased the 7p22 LOD score to a nonsignificant level of 3.09 and split the 15q25 QTL into two loci, one minor QTL on 15q22 (LOD = 2.73) that spanned the LIPC gene, and the other at 15q25 (LOD = 5.63). A family-based quantitative transmission disequilibrium test (QTDT) revealed significant association between variant rs1800588 in LIPC and HDL-C in the GeneQuest population (P = 0.0067), which may account for the minor QTL on 15q22. The 15q25 QTL is the most significant locus identified for HDL-C to date, and these results provide a framework for the ultimate identification of the underlying HDL-C variant and gene on chromosomes 15q25, which will provide insights into novel regulatory mechanisms of HDL-C metabolism.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 血浆高密度脂蛋白胆固醇水平(高密度脂蛋白-C)是冠状动脉疾病(CAD)的独立预测因子。我们已经完成了一项全基因组的高密度脂蛋白-C连锁扫描，研究对象是由388个早产儿冠心病(GeneQuest)多基因家系组成的美国队列。以性别、年龄为协变量，GeneQuest中高密度脂蛋白胆固醇的遗传度为0.37(P=5.1×10(-4))。在7p22和15q25染色体上发现了两个经年龄和性别调整的对数转化高密度脂蛋白基因座(QTL)，其最大多点优势对数(LOD)分别为3.76和6.69。精细定位使7p22的LOD得分降低至3.09，且将15q25的QTL分成两个座位，一个位于15q22(LOD=2.73)，另一个位于15q25(LOD=5.63)。基于家系的数量传递不平衡检验显示，LIPC中的rs1800588变异与GeneQuest群体中的高密度脂蛋白胆固醇显著相关(P=0.0067)，这可能解释了15q22上的小QTL。15q25 QTL是迄今发现的对高密度脂蛋白胆固醇最重要的基因座，这些结果为最终确定染色体15q25上潜在的高密度脂蛋白胆固醇变异和基因提供了一个框架，这将为深入研究高密度脂蛋白胆固醇代谢的新调控机制提供新的见解。