GENETICS OF ATHEROSCLEROSIS IN MEXICAN AMERICANS

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。子项目和 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。 目的：该计划项目支持圣安东尼奥家庭心脏研究，这是一项关于墨西哥裔美国人动脉粥样硬化及其相关性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化的新多态性基因。 研究方法：超过1400名成员的41个扩展的墨西哥裔美国人的家庭被招募，而不考虑疾病状况，并在第一批期间（SAFHS 1）进行了检查，850名成员的较大的家庭被召回在当前的补助金期间（SAFHS 2）。 所有家庭成员的基因分型为414标记在10厘摩地图将完成本补助期结束。 使用来自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、促肾上腺皮质激素原、胰岛素、2小时葡萄糖、LDL 3-C、HDL-C、HDL 2a未酯化胆固醇、中位HDL颗粒大小的几种测量、P-选择素和VCAM-1的数量性状基因座（QTL）。 对于具有最强连锁证据的区域，正在对额外的、更紧密间隔的标记进行类型化，以用于更精细比例的作图策略。 临床相关性：随着对其余家庭成员的基因组扫描的完成，我们准备利用过去10年中创造的宝贵资源。 在拟议的授权期（SAFHS 3），我们将寻求映射和表征现有表型的QTL，这些表型在较小的数据集中没有检测到强信号，以及在召回期间评估的新表型。 我们将追求我们最有希望的线索，精炼连锁信号，表征这些基因的相互作用和多效性效应，并识别它们。 我们还将针对脂肪-岛叶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，将在召回的859个家庭成员进行评估。 利用我们5年和10年的纵向数据，我们将寻找影响CVD危险因素中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 Family 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.