STUDIES IN CARDIOVASCULAR DISEASE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。我们已经完成了一个全基因组的HDL-C连锁扫描在美国队列组成的388个多个家庭与过早的CAD（GeneQuest）。GeneQuest中HDL-C的遗传度为0.37，性别和年龄为协变量（P = 5.1 x 10（-4））。两个主要的数量性状基因座（QTL）的对数转换HDL-C调整的年龄和性别被确定到染色体7 p22和15 q25的最大多点对数的优势（LOD）得分分别为3.76和6.69。精细作图将7 p22的LOD分数降低到3.09的非显著水平，并将15 q25 QTL分成两个位点，一个位于15 q22（LOD = 2.73）的跨越LIPC基因的次要QTL，另一个位于15 q25（LOD = 5.63）。基于家系的定量传递不平衡检验（QTDT）显示，GeneQuest群体中LIPC和HDL-C的变异rs 1800588之间存在显著关联（P = 0.0067），这可能解释了15 q22上的次要QTL。15 q25 QTL是迄今为止对HDL-C鉴定的最重要的位点，这些结果为最终鉴定染色体15 q25上的潜在HDL-C变体和基因提供了框架，这将为HDL-C代谢的新调控机制提供见解。

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.