GENETIC EPIDEMIOLOGY OF BLOOD LIPIDS AND OBESITY--NGHS

血脂与肥胖的遗传流行病学

• 批准号: 2222471
• 负责人: SUE Y.S. KIMM
• 金额: $ 26.76万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2222471
• 关键词: African American; adipose tissue; alleles; apolipoproteins; blood lipid; body composition; cardiovascular disorder epidemiology; caucasian American; coronary disorder; electrofocusing; female; gel electrophoresis; gene frequency; genetic polymorphism; genotype; human genetic material tag; human puberty; human subject; lipid metabolism; longitudinal human study; obesity; polymerase chain reaction; racial /ethnic difference; southern blotting

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.

该项目的目的是进行一项遗传流行病学研究 黑白女孩的冠心病（CHD）危险因素 正在进行的NHLBI赞助的纵向研究 青春期期间肥胖的发展。 NHLBI增长和健康研究， NGHS是2,379名黑白女孩的流行病学研究，年龄在9-10岁 在过去的四年中，每年都在进入年数年。 目前，第0年的随访正在完成，还有2年 计划进行后续。 04年底的队列保留率 是原始队列的91％。 我们提出的研究是独立的 研究项目是对NGHS的辅助研究 利用可用的广泛生物学和环境信息 来自NGHS核心数据库。 我们建议从 1,750名女孩在第7年的后续考试中看到，以确定 那些已知与脂质代谢有关的基因型的基因型 肥胖。 蛋白[载脂蛋白C-II，D和E和LP（A）]和DNA [载脂蛋白B，脂蛋白脂肪酶（LPL）和LDL受体]将是 分析。 我们将确定遗传变异的分布 每个种族。 我们还将估算每个基因型的影响 载脂蛋白定量水平和候选基因基因座和 脂蛋白，以及在体内脂肪的程度和分布之后 调整伴随变量（例如年龄，生物学成熟 每个族裔中的肥胖）。 通过比较频率 在候选基因座的基因型中，我们将能够评估其等位基因 影响及其对黑色血脂和肥胖发育的影响 和白人女性。 因此，我们的研究有可能识别 那些可能参与确定黑/白色差异的基因 在脂质代谢和肥胖症中。 这是一个令人兴奋的领域 几乎没有可用的信息。 最后，我们的研究将启用 我们检查基因变异对定量变化的影响 在不同阶段的血脂水平以及体内脂肪的水平 青春期以来，NGHS方案包括年度人体测量学和 成熟评估和双年度血脂测定以及 广泛的环境措施，包括饮食，家庭和 社会心理信息。 我们的研究是一项独特的研究，因为 极少数机会在2个种族的大量队列中进行遗传分析 有一个非常丰富的数据库的儿童组。 因此，我们 有一个难得的儿童调查的机会：1） 已知与脂质代谢和肥胖有关的基因型； 2） 遗传变异在两个族裔中的分布 参加NGHS； 3）特定的可能作用 青春期期间血脂和体内脂肪变化的基因型。