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。子项目和 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。 血浆高密度脂蛋白胆固醇水平 (HDL-C) 是冠状动脉疾病 (CAD) 的独立预测因子。我们已经在美国队列中完成了 HD​​L-C 的全基因组连锁扫描，该队列由 388 个患有早发 CAD 的多重家族组成 (GeneQuest)。以性别和年龄为协变量时，GeneQuest 中 HDL-C 的遗传率为 0.37 (P = 5.1 x 10(-4))。根据年龄和性别调整的对数转化 HDL-C 的两个主要数量性状基因座 (QTL) 在染色体 7p22 和 15q25 上被鉴定，最大多点对数 (LOD) 分数分别为 3.76 和 6.69。精细作图将 7p22 LOD 得分降低至不显着的水平 3.09，并将 15q25 QTL 分成两个位点，一个次要 QTL 位于 15q22 (LOD = 2.73) 上，跨越 LIPC 基因，另一个位于 15q25 (LOD = 5.63)。基于家族的定量传递不平衡检验 (QTDT) 揭示了 LIPC 中的变体 rs1800588 与 GeneQuest 群体中的 HDL-C 之间存在显着相关性 (P = 0.0067)，这可能是 15q22 上的次要 QTL 的原因。 15q25 QTL 是迄今为止确定的 HDL-C 最重要的位点，这些结果为最终鉴定 15q25 染色体上的潜在 HDL-C 变异和基因提供了框架，这将为 HDL-C 代谢的新调控机制提供见解。