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（由申请方提供）：正如本RFA所强调的，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，如肥胖和葡萄糖耐量受损）的患病率一直在以流行病的比例增加，特别是在少数群体中，如墨西哥裔美国人。然而，儿童MS的潜在机制尚不清楚，也不清楚儿童MS的前体是否与成人相同。如果是这样的话，尝试在儿童中建立MS的前体以及开发可以帮助识别在以后的生活中有MS风险的儿童的生物标志物和/或遗传标志物，对于制定预防或治疗MS高风险儿童的有效策略至关重要。 该提案的目的是确定墨西哥裔美国儿童MS的前体。鉴于T2 DM家族史是与MS风险相关的重要因素，通过检查先前建立的成年家庭队列（如我们的队列，其中富含前驱糖尿病和糖尿病个体）的儿童，可以大大推进在儿童中建立MS前体的计划。我们的设计的额外优势包括在成人中容易获得的MS相关数据，以及已经定位的含有MS基因的基因组区域。在这方面，我们计划检查750名儿童，在我们正在进行的圣安东尼奥家庭出生体重研究中，代表不同家庭的成年人（6-17岁），他们是三个成熟的墨西哥裔美国人家庭研究的原始参与者，以确定MS的前体。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，检查代表不同家庭的750名儿童（6-17岁）成年人，以测量各种MS相关表型（例如，肥胖、葡萄糖耐量受损、血脂异常和高血压）和环境因素如体力活动和健身; 2）将儿童的MS风险特征与我们的家庭研究中已经在成人中建立的MS风险特征进行比较，以使用不同的分析工具（包括NCEP/ATP III对MS的定义）验证儿童和成人之间MS的病因机制是否不同，因子分析和双变量遗传分析;和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，这些遗传标记从我们主要从我们正在进行的连锁/关联分析中识别的25个关键位置基因和其他候选基因中的每一个中选出，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MS在墨西哥裔美国人，儿童和成人。