GENETIC EPIDEMIOLOGY OF BLOOD LIPIDS AND OBESITY

该项目的目标是进行遗传流行病学研究， 冠心病（CHD）的危险因素在黑人和白色女孩， 正在参加一项由NHLBI赞助的纵向研究， 青春期肥胖的发展。 NHLBI生长与健康研究， NGHS是一项对2,379名9-10岁黑人和白色女孩的流行病学研究 入组时的年龄，在过去4年中每年随访一次。 目前，正在完成第0年随访， 计划采取后续行动。 04年末的队列留存率 是原始人群的91% 我们提出的研究是一项独立的 研究项目是NGHS的辅助研究， 利用广泛的生物和环境信息 从NGHS核心数据库。 我们建议从以下人员采集血液样本 在7年级对1 750名女孩进行了随访检查，以确定 在那些已知与脂质代谢有关的基因座上的基因型， 肥胖 蛋白质[载脂蛋白C-II、D和E以及LP（a）]和DNA [载脂蛋白B、脂蛋白脂酶（LPL）和LDL受体]将被 分析了 我们将确定遗传变异的分布， 每个民族。 我们还将估计基因型在每个阶段的影响 载脂蛋白定量水平的候选基因位点， 脂蛋白，也对身体脂肪的程度和分布后， 调整伴随变量（如年龄、生物成熟度 阶段性肥胖）。 通过比较 在候选基因座的基因型，我们将能够评估他们的等位基因 影响及其对血脂和肥胖发展的影响 和白色女性。 因此，我们的研究有可能确定 这些基因可能与决定黑人/白色人的差异有关 在脂质代谢和肥胖症中的作用。 这是一个令人兴奋的领域， 几乎没有可用的信息。 最后，我们的研究将使 我们研究基因变异对数量变化的影响， 血脂水平以及在不同阶段的身体脂肪 由于NGHS协议包括每年的人体测量和 成熟评估和沿着的两年一次的血脂测定， 广泛的环境措施，包括饮食，家庭， 心理社会信息 我们的研究是一项独特的研究，因为 在2个种族的大型队列中进行遗传分析的难得机会 有着丰富数据库的儿童群体。 因此我们 有一个难得的机会，在儿童调查：1）的作用， 已知与脂质代谢和肥胖相关的基因型; 2） 两个民族的遗传变异分布 参与NGHS;以及3）具体的可能作用 基因型对青春期血脂和体脂变化的影响。

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.