GENETIC EPIDEMIOLOGY OF BLOOD LIPIDS AND OBESITY--NGHS

该项目的目标是进行一项遗传流行病学研究 黑人和白人女孩患冠心病的危险因素 正在参与由NHLBI赞助的一项正在进行的纵向研究 青春期肥胖的发展。NHLBI生长与健康研究， NGHS是一项针对2379名9-10岁黑人和白人女孩的流行病学研究 在过去的4年里，每年都对这些人进行跟踪调查。 目前，第0年的后续工作正在完成，另外两年 后续工作正在计划中。04年底的队列保留率 是原始队列的91%。我们提议的研究是一项独立的 作为NGHS的辅助研究的研究项目，以及 利用现有的广泛的生物和环境信息 来自NGHS核心数据库。我们建议从以下地点获取血液样本 在7年级的后续检查中看到了1750名女孩，以确定 已知与脂代谢有关的基因座上的基因型别 肥胖。蛋白质[载脂蛋白C-II、D、E和Lp(A)]和DNA [载脂蛋白B、脂蛋白脂酶(LPL)和低密度脂蛋白受体] 分析过了。我们将确定遗传变异在 每一个民族。我们还将估计在每种情况下基因型的影响 载脂蛋白和载脂蛋白数量水平上的候选基因座 脂蛋白，也对体脂的程度和分布 调整伴随变量(如年龄、生物成熟度 阶段肥胖症)在每个民族内。通过比较频率 ，我们将能够评估它们的等位基因 黑色人种对血脂和肥胖发展的影响及其影响 和白人女性。因此，我们的研究有可能确定 那些可能与决定黑人/白人差异有关的基因 在脂肪代谢和肥胖方面。这是一个令人兴奋的领域，在这里 几乎没有可用的信息。最后，我们的研究将使 美国将检查基因变异对数量变化的影响 不同发育阶段血脂及体脂水平的变化 青春期，因为NGHS协议包括年度人体测量和 成熟度评估和两年一次的血脂测定以及 广泛的环境措施，包括饮食、家庭和 心理社会信息。我们的研究是一项独特的研究，因为 在两个民族的大队列中进行基因分析的难得机会 拥有非常丰富的数据库的儿童群体。因此，我们 有一个难得的机会在儿童中调查：1)角色 已知的与脂代谢和肥胖相关的基因类型；2) 遗传变异在两个民族的分布 参与NGHS；以及3)特定的 青春期血脂和体脂基因分型变化。

The goal of this project is to conduct a genetic epidemiologic study of coronary heart disease (CHD) risk factors in black and white girls who are participating in an ongoing NHLBI-sponsored longitudinal study of obesity development during pubescence. NHLBI Growth and Health Study, NGHS, is an epidemiologic study of 2,379 black and white girls, ages 9-10 years at entry, who have been followed annually for the past 4 years. Currently, Year 0 follow-up is being completed, and 2 more years of follow-up are planned. The cohort retention rate at the end of Year 04 was 91% of the original cohort. Our proposed study is an independent research project which is an ancillary study to the NGHS and which utilizes the extensive biological and environmental information available from the NGHS core data base. We propose to obtain blood samples from 1,750 girls seen at their followup examinations in Year 7, to determine genotypes at those loci known to be implicated in lipid metabolism and obesity. Both protein [apolipoproteins C-II, D, and E and LP(a)] and DNA [apolipoprotein B, lipoprotein lipase (LPL), and LDL receptor] will be analyzed. We will determine the distribution of genetic variation within each ethnic group. We will also estimate the effects of genotype at each candidate gene locus on quantitative level of apolipoproteins and lipoproteins, and also on the degree and distribution of body fat after adjusting for concomitant variables (such as age, biologic maturation stage adiposity) within each ethnic group. By comparing the frequencies of genotypes at candidate loci, we will be able to assess their allelic effects and their impact on blood lipids and obesity development in black and white females. Thus, our study has the potential for identifying those genes which may be involved in determining black/white differences in lipid metabolism and obesity. This is an exciting area in which there is virtually no available information. Finally, our study will enable us to examine the effects of gene variation on changes in quantitative levels of blood lipids as well as in body fat during different stages of pubescence since the NGHS protocol includes annual anthropometric and maturation assessments and biannual blood lipid determinations along with extensive environmental measures which include dietary, household, and psychosocial information. Our study is a unique study because of the rare opportunity to do genetic analyses in a large cohort of 2 ethnic groups of children on whom a very rich data base is available. Thus, we have a rare opportunity to investigate in children: 1) the role of genotypes known to be associated with lipid metabolism and obesity; 2) the distribution of genetic variation in the 2 ethnic groups participating in the NGHS; and 3) the possible roles of specific genotypes on blood lipid and body fat changes during pubescence.