GENETICS OF CORONARY CALCIFICATION IN MEXICAN AMERICANS

墨西哥裔美国人冠状动脉钙化的遗传学

• 批准号: 7718712
• 负责人: HANNA E ABBOUD
• 金额: $ 0.01万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718712
• 关键词: Acceleration; Affect; Arterial Fatty Streak; Atherosclerosis; Cardiac; Cardiovascular Diseases; Chronic Disease; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Death Rate; Development; Diabetes Mellitus; Diabetic Nephropathy; End stage renal failure; Etiology; Event; Family; Funding; General Population; Genes; Genetic; Genetic Predisposition to Disease; Genome; Genome Scan; Grant; Heritability; Institution; Investigation; Kidney Diseases; Knowledge; Lead; Localized; Location; Measures; Metabolic Diseases; Methods; Mexican Americans; Microalbuminuria; Minority; Morbidity - disease rate; Nature; Non-Insulin-Dependent Diabetes Mellitus; Nuclear Family; Participant; Patients; Phenotype; Population; Predisposition; Prevalence; Preventive; Proteinuria; Research; Research Personnel; Resources; Risk; Screening procedure; Severities; Siblings; Source; Susceptibility Gene; Therapeutic; United States National Institutes of Health; Variant; X-Ray Computed Tomography; calcification; cardiovascular disorder risk; clinically relevant; coronary artery calcification; diabetic; disease phenotype; genetic linkage analysis; genome wide association study; macroalbuminuria; mortality; non-diabetic; pleiotropism; proband; size; trait

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: Coronary artery calcification (CAC) is an integral part of atherosclerotic plaque and is an independent predictor of cardiac events. The mortality risk from cardiovascular disease (CVD) in diabetic patients is 2-5 fold greater compared to the general population. The development of diabetic nephropathy (DN) leads to further acceleration of atherosclerosis and a significant increase in morbidity and mortality from CVD. As diabetic patients progress from microalbuminuria to overt proteinuria and ultimately to end stage renal disease (ESRD), there is a parallel increase in death rate from CVD. In this study, we plan to evaluate the atherosclerotic burden by measuring CAC by Multidetector Computed Tomography (MDCT) and to conduct a genetic epidemiological investigation of CAC in a minority population prone to complex disease phenotypes including type 2 diabetes mellitus (T2DM), DN, and CVD. RESEARCH PLAN AND METHODS: We are one of eight Participating Investigation Centers (PICs) of the Family Investigation of Nephropathy of Diabetes (FIND) study, which aims to localize genes for DN using concordant and discordant sibpair analytical approach. Our center completed recruitment of 1200 subjects ascertained from 320 families of Mexican American origin. A majority of thes families are nuclear in nature, composed mainly of sibships with varying sizes. The proband contains diabetic siblings with various phenotypes: normoalbuminuria, microalbuminuria and macroalbuminuria are included in the study. Also included in the study are the nondiabetic siblings of the probands. The overall hypothesis of this proposal is that susceptibility to the development and the severity of CAC in patients with DM and DN has genetic predisposition. In this proposal, we plan to recall all available participants of the FIND subpopulation ascertained by the San Antonio PIC: 1) to measure prevalence and severity of CAC; 2) to determine its heritability; 3) to identify chrmomsomal regions harboring CAC susceptibility genes using genome wide scan and linkage approaches; 3a) Detect initial evidence of linkage to CAC susceptibility loci across the traits, and already available FIND-San Antonio PIC genome scan data; 3b) Refine the initial screening using multipoint variance components method; 3c) Conduct multivariate linkage analysis to identify genetic locations with common genetic influences (pleiotropy) on a given trait-pair e.g., CAC and DM.; and 3d) Perform Oligogenic linkage analysis. CLINICAL RELEVANCE: Diabetes mellitus is a common chronic illness that affects 10-16 million people in the U.S. and is associated with high levels of morbidity and mortality. The results from this project will clarify the contribution of genetic factors to the etiology of CAC. Specifically, this study will lead to the identification of genes that influence variation in CAC. Also, it will lead to the identification of susceptibility loci across the genome with common genetic influences on CAC and its correlated metabolic diseases such as DM and DN. The identification of susceptibility genes for CAC should increase the knowledge about the CVD risk for whom intensive preventive or therapeutic measures may be most beneficial. Screening and identifying patients at risk for CAC will contribute to the current efforts directed to reduce mortality and morbidity of cardiovascular disease.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 目的：冠状动脉钙化（CAC）是动脉粥样硬化斑块的组成部分，是心脏事件的独立预测指标。 与普通人群相比，糖尿病患者心血管疾病（CVD）的死亡率风险高2-5倍。 糖尿病性肾病（DN）的发展导致动脉粥样硬化进一步加速，并显着增加CVD的发病率和死亡率。 随着糖尿病患者从微珠尿症到明显的蛋白尿以及最终终止肾脏疾病（ESRD）的发展，CVD的死亡率平行提高。 在这项研究中，我们计划通过测量多探测器计算机断层扫描（MDCT）测量CAC来评估动脉粥样硬化负担，并对容易发生复杂疾病表型的CAC进行遗传流行病学研究，包括2型糖尿病，包括2型糖尿病，Mellitus（T2DM），DN和CVD。 研究计划和方法：我们是糖尿病肾病（FIND）研究的八个参与调查中心（PIC）之一，该研究旨在使用一致和不和谐的Sibpair分析方法来定位DN的基因。 我们的中心完成了从320个墨西哥裔美国人家庭确定的1200名受试者的招聘。 大多数这些家族本质上都是核，主要由大小不同的sibship组成。 该研究中包含具有各种表型的糖尿病兄弟姐妹：Normoalbuminuria，Microalbuminuria和acaroalbmininuria包括在研究中。 研究中还包括概率的非糖尿病兄弟姐妹。 该提议的总体假设是，DM和DN患者对CAC发育的敏感性和严重程度具有遗传倾向。 在此提案中，我们计划回顾圣安东尼奥图片确定的所有发现亚种群的参与者：1）衡量CAC的患病率和严重性； 2）确定其遗传力； 3）使用基因组广泛的扫描和连锁方法鉴定具有CAC易感基因的Chromomal区域； 3A）检测到与CAC易感性基因座连接的初始证据，并且已经可用的是Antonio PIC基因组扫描数据； 3b）使用多点方差组件方法来完善初始筛选； 3C）进行多元链接分析，以鉴定给定特征对（例如CAC和DM。和3D）执行寡聚键分析。 临床相关性：糖尿病是一种常见的慢性疾病，影响了美国的100-16万人，并且与高水平的发病率和死亡率有关。 该项目的结果将阐明遗传因素对CAC病因的贡献。 具体而言，这项研究将导致鉴定影响CAC变异的基因。 此外，这将导致对整个基因组的易感基因座的鉴定，并具有对CAC及其相关代谢疾病（例如DM和DN）的常见遗传影响。 识别CAC易感基因的识别应增加有关CVD风险的知识，而该风险的强化预防或治疗措施可能是最有益的。 筛查和识别有CAC风险的患者将有助于当前致力于降低心血管疾病的死亡率和发病率的努力。