The Metabolic Syndrome in Mexican American Children

描述(由申请人提供)：正如本RFA强调的那样，超重/肥胖、2型糖尿病(T2 DM)和代谢综合征(MS：一系列代谢异常，如肥胖和糖耐量受损)的患病率一直在以流行的比例增加，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，儿童多发性硬化症的前体是否与成人的多发性硬化症相同也不清楚。如果是这样的话，试图在儿童中建立多发性硬化症的前体，以及开发生物标志物和/或遗传标记，以帮助识别未来生活中患有多发性硬化症的儿童，对于制定有效的策略来预防或治疗多发性硬化症的高危儿童是至关重要的。 这项建议的目的是建立墨西哥裔美国儿童多发性硬化症的先兆。鉴于T2 DM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族队列的儿童(如我们的队列)，可以极大地推进在儿童中建立MS前体的计划，这些队列中有丰富的糖尿病前期和糖尿病个体。我们设计的其他优势包括容易获得的成人多发性硬化症相关数据，以及已经定位的包含多发性硬化症基因的基因组区域。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出生体重研究中检查代表不同家庭的750名儿童(6-17岁)，他们是三个成熟的墨西哥裔美国家庭研究的原始参与者，以建立MS的先兆。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检查750名代表不同家庭的儿童(6-17岁)，以测量各种与MS相关的表型(例如肥胖、糖耐量受损、血脂异常和高血压)以及环境因素，如体力活动和健康；2)比较儿童和成人的MS风险分布，以验证儿童和成人之间是否存在不同的MS发病机制，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；以及3)检查儿童MS表型与10个遗传标记(单核苷酸多态，SNPs)之间的关联，这些遗传标记是从我们已经确定的25个关键位置和其他候选基因中的每一个中挑选出来的，主要是通过我们正在进行的连锁/关联分析，这些基因可能会影响成人的MS表型。总之，这项研究提供了一个难得的机会，有助于更好地了解墨西哥裔美国人的多发性硬化症，无论是儿童还是成年人。

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.