The Metabolic Syndrome in Mexican American Children

墨西哥裔美国儿童的代谢综合症

• 批准号: 7024501
• 负责人: RAVINDRANATH DUGGIRALA
• 金额: $ 49.25万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7024501
• 关键词: Mexican Americans; adolescence (12-20); biomarker; clinical research; diabetes risk; disease /disorder etiology; epidemiology; genetic markers; human birth weight; human subject; metabolic syndrome; middle childhood (6-11); noninsulin dependent diabetes mellitus; phenotype; single nucleotide polymorphism

DESCRIPTION (provided by applicant): As this RFA emphasizes, the prevalence rates of overweight/obesity, type 2 diabetes (T2DM), and the Metabolic Syndrome (MS: a constellation of metabolic abnormalities such as obesity and impaired glucose tolerance) have been increasing at epidemic proportions, particularly in minority groups such as Mexican Americans. However, the mechanisms that underlie the MS in children are unclear, and it is also not clear whether or not the precursors of the MS in children are the same as those in adults. If so, attempts to establish the precursors of the MS in children as well as to develop biomarkers and/or genetic markers that could help identify children at risk for the MS later in life, are of the utmost importance in developing effective strategies to prevent or treat children that are at high risk for the MS. The purpose of this proposal is to establish the precursors of the MS in Mexican American Children. Given that family history of T2DM is an important factor associated with the MS risk, plans to establish the precursors of the MS in children could be greatly advanced by examining the children of previously established adult family-based cohorts such as ours that are enriched with prediabetic and diabetic individuals. Added advantages of our design include the readily available MS-related data in adults, and already localized genomic regions that harbor the MS genes. In this context, we plan to examine 750 children (aged 6-17 years) of the adults representing distinct families in our ongoing San Antonio Family Birth Weight Study, who are the original participants of the three well-established Mexican American family studies, to establish the precursors of MS. The major goals of this project are: 1) to examine 750 children (aged 6-17) years of the adults representing various families in our ongoing San Antonio Birth Weight Study in order to measure various MS-related phenotypes (e.g., obesity, impaired glucose tolerance, dyslipidemia, and hypertension) and environmental factors such as physical activity and fitness; 2) to compare the MS risk profiles of the children to those already established in the adults of our family studies to verify whether or not the etiological mechanisms underlying the MS are different between children and adults using different analytical tools including the NCEP/ATPIII definition of the MS, factor analysis, and bivariate genetic analysis; and 3) to examine the association between MS phenotypes in children and 10 genetic markers (single nucleotide polymorphisms, SNPs) selected from each of 25 key positional and other candidate genes that we have identified, primarily from our ongoing linkage/association analyses, as potentially influencing MS phenotypes in adults. In sum, this study provides an unusual opportunity to contribute to a better understanding of the MS in Mexican Americans, both children and adults.

描述（由申请人提供）：正如此RFA所强调的那样，超重/肥胖症的患病率，2型糖尿病（T2DM）和代谢综合征（MS：代谢异常的星座，例如肥胖和肥胖症耐受性诸如葡萄糖的耐受性，尤其是在较小的小组中，诸如肥胖症和葡萄糖耐受性受损）在较小的小组中越来越高。但是，儿童中MS的基础的机制尚不清楚，也不清楚儿童中MS的前体是否与成年人中的MS前体相同。如果是这样，试图在儿童中建立MS的前体，以及开发生物标志物和/或遗传标记，这些标记和/或遗传标志物可以帮助识别生命后期的MS风险的儿童，对于制定有效的策略来预防或治疗有MS高风险的儿童至关重要。 该提议的目的是在墨西哥裔美国儿童中建立MS的先驱。鉴于T2DM的家族史是与MS风险相关的重要因素，因此可以通过检查以前建立的成人基于家庭的同类同伙（例如我们的人）的儿童来建立儿童中MS的前体的计划，这些儿童具有丰富的糖尿病和糖尿病患者。我们设计的增加的优势包括成人中随时可用的MS相关数据，以及具有MS基因的局部基因组区域。在这种情况下，我们计划在我们正在进行的圣安东尼奥家庭体重研究中检查750名代表不同家庭的成年人（6-17岁）的儿童，他们是三位墨西哥裔美国人家庭研究的原始参与者，以建立MS的前代。该项目的主要目标是：1）在我们正在进行的圣安东尼奥体重研究中代表各种家庭的750名儿童（6-17岁），以衡量各种与MS相关的表型（例如肥胖症，肥胖，炎症性葡萄糖耐受性，血脂异常和血脂异常和高血压和环境因素和体力系统因素和体能因素和体能因素和体力系统差异）； 2）将儿童的MS风险谱与我们家庭研究成年人中已经建立的患者的MS风险谱进行比较，以验证儿童和成人使用不同的分析工具（包括NCEP/ATPIII的定义）在儿童和成年人之间是否有不同的病因机制不同； 3）检查儿童中MS表型与10个遗传标记（单核苷酸多态性，SNP，SNP）之间的关联，我们从25个关键位置和其他候选基因中的每一个中选择了我们所识别的，主要是从我们正在进行的链接/关联分析中，作为成人的潜在影响MS表型。总而言之，这项研究为对墨西哥裔美国人（包括儿童和成人）的MS更好地理解提供了一个异常的机会。