Maternal Obesity, Fetal Genomics, and Atherosclerotic Metabolic Risk

母亲肥胖、胎儿基因组学和动脉粥样硬化代谢风险

• 批准号: 7290437
• 负责人: DAVID Stuart SISCOVICK
• 金额: $ 41.87万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-25 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7290437
• 关键词: Accounting; Address; Adipocytes; Adolescent; Adrenal Glands; Adult; Age; Biological Neural Networks; Birth; Birth Weight; Breast Feeding; Build-it; Candidate Disease Gene; Cardiovascular system; Characteristics; Childhood; Clinical; Collaborations; Data; Desire for food; Development; Diabetes Mellitus; Diabetic intrauterine environment; Dyslipidemias; Environment; Environmental Risk Factor; Fetal Development; Fetal Growth; Genetic; Genetic Variation; Genomics; Gestational Age; Goals; Growth; High Blood Pressure; Homeostasis; Human; Hypertension; Hypothalamic structure; Institution; International; Intervention; Lead; Measures; Metabolic; Metabolic Diseases; Modeling; Molecular; Mothers; Obesity; Pathway interactions; Perinatal; Pituitary Gland; Population; Pregnancy; Range; Recruitment Activity; Research; Research Personnel; Risk; Series; Universities; Variant; Washington; Weight Gain; base; cohort; design; fetal; follow-up; hypercholesterolemia; hypothalamic-pituitary-adrenal axis; insulin sensitivity; insulin signaling; maternal cigarette smoking; postnatal; prenatal; prevent; programs; response; young adult

DESCRIPTION (provided by applicant): There is mounting evidence that maternal obesity (MO) influences both fetal development and adult atherosclerotic metabolic risk (AMR), due to obesity-related metabolic diseases, such as diabetes, hypercholesterolemia, and high blood pressure. However, the mechanisms that account for the associations of MO with AMR remain unknown. Using data from a unique, population-based, birth cohort and a 30-year follow-up examination, we propose to examine (1) whether the association of MO and AMR is due, at least in part, to common maternal and/or fetal genetic variation in a set of candidate genes from distinct molecular pathways, and (2) whether maternal and/or fetal genetic variation influences the MO- AMR relation through an effect on the intra-uterine environment and fetal growth. The Jerusalem Perinatal Study (JPS) collected extensive prenatal, perinatal, and postnatal data from births from 1974-76. We now propose to add new phenotypic and genotypic data from mothers and offspring to the existing archival data. We will recruit a sub-cohort of mothers (n =1500) and their offspring born from 1974-76 (n = 1500), reflecting the full range of MO and BW. We will determine whether maternal and fetal genetic variation in sets of candidate genes in molecular pathways, such as insulin sensitivity and insulin signaling, adipocyte homeostasis and hypothalamic-pituitary-adrenal (HPA) axis, and the appetite regulatory neural network, account for the associations of MO with AMR in young adults, ages 30-32, through an effect on intra- uterine growth. In a series of nested models, we will distinguish the effects of common maternal and fetal genetic variation that has the potential to alter the intra-uterine environment, from post-natal effects of offspring genetic variation and non-genetic effects of MO on adult AMR, after taking into account the effects of other factors, such as maternal smoking and breast feeding. We also will examine potential interactions of MO with maternal and fetal genetic variation on the development of AMR. The research is designed to explore several promising mechanistic pathways, using measures of human maternal and fetal genomic variation, in the context of MO, intra-uterine growth, and other pre- and post-natal clinical characteristics. The long-term goals of the proposed study are to identify potential mechanistic targets for interventions to prevent the consequences of MO on the intra-uterine environment and adult AMR.

描述（由申请人提供）：有越来越多的证据表明，由于与肥胖相关的代谢性疾病，例如糖尿病，高胆固醇血症和高血压，孕产妇肥胖（MO）都会影响胎儿发育和成人动脉粥样硬化代谢风险（AMR）。但是，解释MO与AMR关联的机制仍然未知。 Using data from a unique, population-based, birth cohort and a 30-year follow-up examination, we propose to examine (1) whether the association of MO and AMR is due, at least in part, to common maternal and/or fetal genetic variation in a set of candidate genes from distinct molecular pathways, and (2) whether maternal and/or fetal genetic variation influences the MO- AMR relation through an effect on the intra-uterine environment and fetal growth.耶路撒冷围产期研究（JPS）从1974 - 76年期间收集了大量产前，围产期和产后数据。现在，我们建议将母亲和后代的新表型和基因型数据添加到现有的档案数据中。我们将招募一组母亲（n = 1500）及其后代从1974 - 76年出生（n = 1500），反映了MO和BW的全部范围。我们将确定分子途径中候选基因集中的母体和胎儿遗传变异是否是否是否是否胰岛素敏感性和胰岛素信号传导，脂肪细胞稳态以及下丘脑 - 垂体 - 肾上腺肾上腺轴（HPA）轴，以及胃口调节性神经网络的效果，年轻人与Moa in Inters contimiations，Moa-Amr-agr-agn-intress Amr-Mo in nigns in Mo Agrys conteriations in Comesiations，Moa-Amr-33。子宫生长。在一系列嵌套模型中，我们将区分常见的母体和胎儿遗传变异的影响，这些变异有可能改变后代遗传变异的产后效应以及MO对成人AMR的非遗传效应的产后影响，并考虑到其他因素（例如母体吸烟和乳房喂养）的影响。我们还将检查MO与母体和胎儿遗传变异对AMR发展的潜在相互作用。该研究旨在使用人类母体和胎儿基因组变异的测量，在MO，北极河内生长以及其他产前和产后临床特征的背景下探索几种有希望的机械途径。拟议研究的长期目标是确定干预措施的潜在机械目标，以防止MO对摩尔河内环境和成人AMR的后果。