GENETICS OF ATHEROSCLEROSIS IN MEXICAN AMERICANS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。目的：该计划项目支持圣安东尼奥心脏研究，这是一项关于墨西哥裔美国人动脉粥样硬化及其相关因素的全面遗传流行病学研究。长期目标是检测、定位、表征和识别影响心血管疾病易感性变异的新的多态基因。研究计划和方法：在不考虑疾病状况的情况下招募了41个墨西哥裔美国大家庭的1400多名成员，并在第一次赠款期间(SAFHS1)进行了检查，并在当前赠款期间(SAFHS2)召回了850名大家庭成员。在当前赠与期结束之前，将完成对10厘米图谱中414个标记的所有家庭成员的基因分型。利用来自10个最大家系(家系集合A)的近500名成员的数据，我们检测并定位了影响瘦素、脂肪质量、BMI、促肾上腺皮质激素原、胰岛素、2小时血糖、低密度脂蛋白3-C、高密度脂蛋白-C、高密度脂蛋白2a、几种测量高密度脂蛋白颗粒中位数、P-选择素和血管细胞黏附分子-1的数量性状基因座(QTL)。对于具有最强连锁证据的地区，正在对额外的、间隔更近的标记进行分类，以用于更精细的比例尺测绘策略。临床意义：随着对其余家庭成员的基因组扫描完成，我们准备利用过去10年创造的宝贵资源。在拟议的授权期内(SAFHS3)，我们将设法定位和表征在较小的数据集中没有检测到强信号的现有表型的QTL，以及在召回期间评估的新表型的QTL。我们将继续寻找我们最有希望的线索，提炼连锁信号，描述这些基因的相互作用和多效性，并识别它们。我们还将针对脂肪-岛轴的新表型以及与炎症和氧化应激相关的表型。这些新的表型，以及葡萄糖、胰岛素、总胆固醇和高密度脂蛋白胆固醇、脂蛋白大小表型和瘦素，将在859名家庭成员的召回中进行评估。利用我们5年和10年的纵向数据，我们将寻找影响心血管疾病风险因素与年龄相关变化的基因。

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. OBJECTIVE: This Program Project supports the San Antonio Heart Study, a comprehensive genetic epidemiological study of atherosclerosis and its correlates in Mexican Americans. The long-term goal is to detect, map, characterize, and identify new polymorphic genes that influence variation in susceptibility to cardiovascular disease. RESEARCH PLAN AND METHODS: More than 1400 members of 41 extended Mexican American families were recruited without regard to disease status and examined during the first grant period (SAFHS1), and 850 members of the larger families were recalled during the current grant period (SAFHS2). Genotyping of all family members for 414 markers in a 10 centimorgan map will be complete by the end of the current grant period. Using data from nearly 500 members of 10 of the largest families (Pedigree Set A), we have detected and mapped quantitative trait loci (QTLs) influencing leptin, fat mass, BMI, pro-ACTH, insulin, 2 hour glucose, LDL3-C, HDL-C, HDL2a unesterified cholesterol, several measures of median HDL particle size, P-selectin, and VCAM-1. For regions with the strongest evidence for linkage, additional, more closely spaced markers are being typed for use in finer scale mapping strategies. CLINICAL RELEVANCE: With the completion of the genome scan for the remaining family members, we are poised to take advantage of the valuable resource created during the past 10 years. In the proposed grant period (SAFHS3), we will seek to map and characterize QTLs for existing phenotypes for which strong signals were not detected in the smaller data set, as well as new phenotypes assessed during the recall. We will pursue our most promising leads, refining linkage signals, characterizing interactions and pleiotropic effects of these genes, and identifying them. We will also target novel phenotypes of the adipo-insular axis and phenotypes related to inflammation and oxidative stress. These new phenotypes, as well as glucose, insulin, total and HDL cholesterol, lipoprotein size phenotypes, and leptin, will be assessed in a recall of 859 family members. Taking advantage of our 5- and 10-year longitudinal data, we will seek genes that influence age-related changes in CVD risk factors.