GENETIC EPIDEMIOLOGY OF BLOOD LIPIDS AND OBESITY--NGHS

描述：（改编自研究者摘要）该项目有两个 主要目标。 第一个是研究遗传变异在 小鼠肥胖、脂肪和生长激素基因的人类同源物， 肿瘤坏死因子α、胆囊收缩素和神经肽Y 肥胖测量中个体间差异的确定，测量 的身体形态，和肥胖的变化，在一个大的birthweight样本， 参加国家心脏、肺和血液研究所生长的女孩 健康研究（NGHS）。 肥胖的衡量标准包括BMI和皮褶， 身体形态的测量是区域脂肪的指标 分布，如腰/臀比例。 研究者将鉴定候选基因座的多态性变异 通过分子筛选，开发基于PCR的基因分型检测方法， 变异，并估计在这些位点的等位基因频率在黑色和 白色女孩。 这些位点的变异与测量之间的关联 将检查每次年度访视时的肥胖率，以及 在主要NGHS的整个9年随访期内， 以来 这些肥胖症候选基因中的几个的产物是推定的 饱腹感因素，研究人员还将研究 这些位点的变化与每餐的总热量含量以及 与进食的行为方面一样， 以及每天摄入的脂肪总量。 第二个主要目标是对基因进行详细分析 参与维持甘油三酯之间的稳态关系 和高密度脂蛋白胆固醇，以进一步了解明显的黑白 甘油三酯和HDL-C水平对增加的反应差异 青春期肥胖症 感兴趣的基因是LCAT、CETP、HL和LPL。 黑人女孩的肥胖程度高于白色女孩， 从9-10岁到15-16岁的女孩，黑人女孩继续有 高水平的HDL。 有一个显着的种族肥胖的相互作用 关于甘油三酯，黑人女孩的水平增加到 比白色女孩的程度要小， 肥胖症 研究人员假设，这种差异的一部分， 血脂水平的差异可能是由于频率的变化 在LCAT、CETP、HL和/或LPL基因座上。 他们将通过以下方式来检验这一假设： 对比这些基因座上变异的频率和等位基因效应， 在黑人和白色女孩中。 拟定研究作为辅助研究嵌套在正在进行的NGHS中 在NGHS的最后一年。 这一辅助机制提供了一个机会， 为了利用包括人体测量的广泛的纵向数据， 饮食，行为和环境措施，收集了这个队列， 10年 由于主要NGHS的目标是调查种族 在青春期肥胖发展的分歧，这个数据库是 特别是对肥胖发展的研究。

DESCRIPTION: (Adapted from Investigator's Abstract) This project has two major objectives. The first is to examine the role of genetic variation in the human homologues of the mouse obese, fat and agouti genes as well as in tumor necrosis factor alpha, cholecystokinin, and neuropeptide Y for the determination of interindividual variation in measures of obesity, measures of body morphology, and changes in adiposity in a large biracial sample of girls participating in the National Heart, Lung, and Blood Institute Growth and Health Study (NGHS). The measures of obesity include BMI and skinfolds, and the measures of body morphology are indicators of regional fat distribution, such as waist/hip ratio. The investigators will identify polymorphic variation at the candidate loci by molecular screening, developing PCR-based assays for genotyping this variation, and estimating allele frequencies at these loci in black and white girls. The association between variation at these loci and measures of adiposity at each annual visit will be examined, as will the changes in adiposity over the entire 9-year follow-up period of the main NGHS. Since the products of several of these obesity candidate genes are putative satiety factors, the investigators also will examine the association of variation at these loci with the total caloric content of each meal as well as with behavioral aspects of eating such as frequency of eating/snacking and the total amount of fat ingested per day. The second major objective is to carry out a detailed analysis of genes involved in maintaining the homeostatic relationship between triglycerides and HDL cholesterol, to further understand the apparent black-white differences in responses of triglyceride and HDL-C levels to increases in adiposity during puberty. The genes of interest are LCAT, CETP, HL and LPL. While adiposity increased to a greater extent in black girls than in white girls from ages 9-10 years to 15-16 years, black girls continue to have higher levels of HDL. There is a significant race-adiposity interaction regarding triglycerides with the levels in black girls increasing to a lesser extent than in white girls who are experiencing the same increase in adiposity. The investigators hypothesize that part of this difference in blood lipid levels may be due to differences in the frequency of variation at the LCAT, CETP, HL, and/or LPL loci. They will test this hypothesis by contrasting the frequencies and allelic effects of variation at these loci in black and white girls. The proposed study is nested within the ongoing NGHS as an ancillary study in the final year of NGHS. This ancillary mechanism offers an opportunity to utilize extensive longitudinal data which encompass anthropometric, dietary, behavioral, and environmental measures collected on this cohort for 10 years. Since the goal of the main NGHS is to investigate racial divergence in adiposity development during pubescence, this database is particularly rich for the investigation of obesity development.