GENETICS OF ATHEROSCLEROSIS IN MEXICAN AMERICANS

墨西哥裔美国人动脉粥样硬化的遗传学

• 批准号: 7378194
• 负责人: JEAN W MACCLUER
• 金额: $ 8.38万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378194
• 关键词: GENETICS; ATHEROSCLEROSIS; MEXICAN; AMERICANS

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.

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。目的：本项目支持圣安东尼奥心脏研究，这是一项墨西哥裔美国人动脉粥样硬化及其相关因素的综合遗传流行病学研究。长期目标是检测、绘制、表征和鉴定影响心血管疾病易感性变异的新多态性基因。研究计划和方法：在第一次资助期（SAFHS1）招募了41个墨西哥裔美国大家庭的1400多名成员，无论其疾病状况如何，并对其进行了检查，在当前资助期（SAFHS2）召回了大家庭的850名成员。所有家庭成员的414个标记的基因分型将在当前资助期结束前完成。利用来自10个最大家族（谱系集A）的近500名成员的数据，我们检测并绘制了影响瘦素、脂肪量、BMI、前acth、胰岛素、2小时葡萄糖、LDL3-C、HDL- c、HDL2a未酯化胆固醇、几种中位HDL颗粒大小、p -选择素和VCAM-1的定量性状位点（qtl）。对于具有最强关联证据的区域，正在键入额外的、间隔更近的标记，以便用于更精细的制图策略。临床意义：随着剩余家族成员基因组扫描的完成，我们准备好利用过去10年创造的宝贵资源。在拟议的拨款期内（SAFHS3），我们将寻求绘制和表征在较小数据集中未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。我们将继续寻找最有希望的线索，完善连锁信号，表征这些基因的相互作用和多效效应，并识别它们。我们还将针对脂肪岛轴的新表型和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，将在召回的859个家庭成员中进行评估。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危险因素年龄相关变化的基因。