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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 血浆HDL胆固醇水平（HDL-C）是冠状动脉疾病（CAD）的独立预测指标。我们已经完成了由388个具有早产CAD（Genequest）的多重多重家族组成的美国队列中HDL-C的全基因组链接扫描。 HDL-C在Genequest中的遗传力为0.37，随着协变量为年龄（P = 5.1 x 10（-4））。针对年龄和性别调整的对数转换的HDL-C的两个主要定量性状基因座（QTL）分别鉴定为染色体上的7p22和15q25，分别为3.76和6.69的最大多点（LOD）得分。精细映射将7p22 LOD得分降低至3.09的不重要水平，并将15q25 QTL分为两个基因座，一个在15q22上的次要QTL（LOD = 2.73）跨越了LIPC基因，而另一个则在15q25（LOD = 5.63）。基于家庭的定量传播不平衡测试（QTDT）显示，LIPC中的变体RS1800588与Genequest人群中的HDL-C之间的显着关联（P = 0.0067），这可能占15q22的次要QTL。 15q25 QTL是迄今为止针对HDL-C确定的最显着的基因座，这些结果为最终鉴定了基础HDL-C变体的最终鉴定和染色体上的基因提供了一个框架，该染色体将提供对HDL-C代谢性HDL-C代谢的新调节机制的见解。