The Metabolic Syndrome in Mexican American Children

描述（由申请人提供）：正如本 RFA 所强调的那样，超重/肥胖、2 型糖尿病 (T2DM) 和代谢综合征（MS：一系列代谢异常，如肥胖和糖耐量受损）的患病率呈流行趋势，特别是在墨西哥裔美国人等少数群体中。然而，儿童多发性硬化症的机制尚不清楚，也不清楚儿童多发性硬化症的前兆是否与成人相同。如果是这样，尝试确定儿童多发性硬化症的前兆，并开发生物标志物和/或遗传标志物，帮助识别以后生活中面临多发性硬化症风险的儿童，对于制定预防或治疗多发性硬化症高风险儿童的有效策略至关重要。 该提案的目的是在墨西哥裔美国儿童中建立 MS 的前身。鉴于 T2DM 家族史是与 MS 风险相关的一个重要因素，通过检查先前建立的成人家庭队列（例如我们的队列中富含糖尿病前期和糖尿病个体）的儿童，可以大大推进确定儿童 MS 前兆的计划。我们设计的额外优势包括容易获得的成人 MS 相关数据，以及已经定位的包含 MS 基因的基因组区域。在这种背景下，我们计划对我们正在进行的圣安东尼奥家庭出生体重研究中代表不同家庭的 750 名成人儿童（6-17 岁）进行检查，他们是三项完善的墨西哥裔美国人家庭研究的原始参与者，以确定多发性硬化症的前兆。该项目的主要目标是： 1) 在我们正在进行的圣安东尼奥出生体重研究中，对代表不同家庭的 750 名儿童（6-17 岁）进行检查，以测量各种与多发性硬化症相关的表型（例如肥胖、糖耐量受损、血脂异常和高血压）以及体力活动和健康等环境因素； 2) 使用不同的分析工具（包括 NCEP/ATPIII 对 MS 的定义、因子分析和双变量遗传分析），将儿童的 MS 风险状况与我们家庭研究中已建立的成人的 MS 风险状况进行比较，以验证儿童和成人之间 MS 的病因机制是否不同； 3) 检查儿童 MS 表型与 10 个遗传标记（单核苷酸多态性，SNP）之间的关联，这些遗传标记选自我们主要通过正在进行的连锁/关联分析确定的 25 个关键位置基因和其他候选基因，这些基因可能影响成人 MS 表型。总之，这项研究提供了一个不寻常的机会，有助于更好地了解墨西哥裔美国人（儿童和成人）的多发性硬化症。

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.