GENETIC EPIDEMILOGY OF ENGERGY METABOLISM IN BLACK GIRLS

描述：非裔美国人(AA)女性肥胖率很高 对公共卫生的重要性，因为再生障碍性贫血妇女死于 心血管疾病和肾脏疾病比白人(W)女性更多。他们的理由是 对肥胖的明显易感性仍然鲜为人知，尽管现在 已知AA女性的静息能量消耗(REE)低于W 女人。我们建议进行一项多管齐下的代谢和遗传流行病学研究 检测与能量代谢有关的两个候选基因(UCP3和b3AR) 尚未在这一高危人群中进行调查。此应用程序 建立在我们之前对150名混血儿队列的研究结果的基础上 19-21岁的年轻女性。我们发现，稀土元素(根据脂肪质量和脱脂情况进行了调整 体重)一直比W低约78千卡/天 所有的肥胖症。此外，AA纯合子妇女的REE较低 UCP3的C等位基因(外显子5)。然而，由于C的相对稀有 在AA等位基因中，我们的样本大小为5个AA纯合子的C等位基因只产生了一个 弱联想，p=0.05。我们建议对600名12-15岁的再生障碍性贫血女孩进行筛查， 使用口腔拭子作为一种非侵入性的DNA获取方法，以确定 UCP3基因分型和b3AR基因分型。我们将招收211名女生， 根据他们的UCP3基因选择，用于测量REE和身体 临床研究受控环境中的成分(使用地塞米松) 在辛辛那提儿童医院。我们将研究稀土元素的变化 UCP3的基因分型和大样本来证实我们之前的 找到了。拟议的2x3设计将允许我们检查 与UCP3变异相关的基因是由于UCP3基因座本身或由于 UCP3和b3AR之间的相加效应或相互作用。这并不是 之前已经考虑过了。我们的研究将有助于更好地理解这一关系 两个重要的能量代谢候选基因UCP3之间的变异 和b3AR，以及个体间稀土元素水平的差异 (肥胖症)风险人群。此应用程序还构建在 PI与研究人员之间建立了良好的合作关系 在辛辛那提儿童医院和费雷尔博士的人类 匹兹堡大学遗传学实验室。因此，所获得的信息 从建议的研究中应该增加我们对情结的理解 种族、遗传、能量代谢与肥胖的相互关系 发展。反过来，这应该有助于推动我们对“节俭”基因的追求， 因为节俭的能量消耗可能是主要的表型表现 属于这种基因的。

DESCRIPTION: The high prevalence of obesity in African-American (AA) women is of public health importance since AA women suffer higher mortality from cardiovascular and renal diseases than do white (W) women. The reason for their marked susceptibility to obesity remains poorly understood though it is now known that AA women manifest lower resting energy expenditure (REE) than W women. We propose a multi-pronged metabolic and genetic epidemiologic study to examine two candidate genes (UCP3 and b3AR) implicated in energy metabolism which have yet to be investigated in this high risk group. This application builds upon the findings from our previous study of a biracial cohort of 150 young women aged 19-21. We showed that REE (adjusted for fat mass and fat-free mass) in AA women was consistently lower than W by about 78 kcal/day across the entire range of adiposity. Further, REE was lower for those AA women homozygous for the C allele of UCP3 (exon 5). However, due to the relative rarity of the C allele among AA, our sample size of 5 AA homozygous for C allele yielded only a weak association, p=0.05. We propose to screen 600 AA girls, aged 12-15 years, using buccal swabs as a non-invasive method of obtaining DNA, to determine their UCP3 genotypes as well as b3AR genotypes. We will recruit 211 girls, selected based on their UCP3 genotype, for measurements of REE and body composition (using DEXA) in a controlled setting of the Clinical Research Center at the Cincinnati Children's Hospital. We will examine variation in REE across the genotypes of UCP3 with a large sample to corroborate our previous finding. The proposed 2x3 design will allow us to examine whether the effects associated with UCP3 variation are due to the UCP3 locus alone or due to the additive effect or interaction between UCP3 and b3AR. This has not been considered before. Our study will help to better understand the relationship between variation in two important candidate genes for energy metabolism, UCP3 and b3AR, and inter-individual variation in the levels of REE in this very high risk (for obesity) population. This application also builds on a well-established collaborative relationship between the PI and the researchers at the Cincinnati Children's Hospital and also with Dr. Ferrell's Human Genetics Laboratory at the University of Pittsburgh. Thus, information obtained from the proposed study should increase our understanding of the complex interrelationship between ethnicity, genetics, energy metabolism, and obesity development. This, in turn, should help advance our quest for "thrifty" genes, since parsimonious energy expenditure may be the main phenotypic manifestation of such a genotype.