Epidemiology & epigenetics: Maternal diet, DNA methylation, & offspring adiposity

流行病学

• 批准号: 7821115
• 负责人: MATTHEW W GILLMAN
• 金额: $ 49.78万
• 依托单位: HARVARD PILGRIM HEALTH CARE, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7821115
• 关键词: 7 year old; Address; Adult; Affect; Age; Animal Experiments; Animals; Area; Behavior; Betaine; Birth; Blood; Blood Cells; Blood Pressure; Blood specimen; Body mass index; Cardiovascular Diseases; Child; Choline; Chronic; Cohort Studies; Conceptions; DNA; DNA Methylation; Data; Development; Diabetes Mellitus; Diet; Environment; Epidemiologic Studies; Epidemiology; Epigenetic Process; Fatty acid glycerol esters; Folate; Funding; Genetic; Genomics; Glucose Intolerance; Goals; Grant; Health; Human; Individual; Insulin Resistance; Intake; Knowledge; Knowledge acquisition; Leptin; Long Interspersed Nucleotide Elements; Longevity; Malignant Neoplasms; Measures; Metabolic; Metabolic Diseases; Methodology; Methylation; Morbidity - disease rate; Obesity; Outcome; Pathway interactions; Phenotype; Physical environment; Physiology; Plasma; Plastics; Population; Pregnancy; Preventive Intervention; Public Health; Research; Research Personnel; Skinfold Thickness; Social Behavior; Species Specificity; Sum; Technology; Time; Tissues; Translating; Triceps Brachii Muscle; Umbilical Cord Blood; Variant; Vitamin B 12; Work; adiponectin; base; cardiovascular risk factor; clinically relevant; cost; critical developmental period; critical period; design; diabetic; fetal; human population study; improved; indexing; mortality; mouse model; next generation; offspring; prenatal; prevent; programs; public health relevance; research study

DESCRIPTION (provided by investigator): This application addresses Challenge Area 08, "Genomics," and Challenge Topic 08-AG-105 (also OD [OBSSR] - 102), "Approaches to study the interactions among individual behaviors, social and physical environments, and genetic/epigenetic processes during critical developmental periods." Decades of animal physiology experiments unequivocally show that perturbations during early, plastic, critical periods of development can have lifelong, sometimes irreversible adverse impact on markers of chronic cardio- metabolic disease like adiposity, blood pressure and glucose intolerance, and on lifespan itself. The field of epigenetics has recently revealed some of the mechanisms underlying these observations. For example, in the yellow agouti mouse model, a maternal diet rich in methyl donors around conception causes DNA methylation of a metastable epiallele, preventing offspring from becoming fat, diabetic, and cancer-prone. No study in human populations, however, has examined pathways from maternal diet in early pregnancy through epigenetic changes to offspring phenotype. The goals of this study are to examine relationships among maternal diet in early pregnancy, particularly variation in intake of methyl donors, global DNA methylation in maternal blood in early and late pregnancy and in umbilical cord blood, and adiposity-related outcomes in 3- and 7-year-old children. We will carry out this project within the well-characterized pre-birth cohort study Project Viva, which is perhaps the only US-based epidemiologic study with the design features to address these aims: prospectively collected, validated, early pregnancy diet information, maternal and cord blood specimens, and research- quality offspring cardio-metabolic phenotype data. Obesity, cardiovascular disease, diabetes, and related conditions are leading causes of morbidity and mortality in the U.S., and their earliest origins exist in behavior and environment during the prenatal period. Adding epigenetic data to existing epidemiologic studies offers the potential to translate knowledge from animal experiments to the human condition as well as to mount preventive interventions. Given the potential scientific and public health impact, the time has come for an influx of funds to advance this area in significant ways quickly, and the Challenge Grants program provides the right vehicle to do so. PUBLIC HEALTH RELEVANCE: The goals of this study are to examine the extent to which maternal diet in early pregnancy affects methylation of maternal and fetal DNA, an epigenetic process; and the extent to which DNA methylation predicts obesity and cardiovascular risk factors in 3- and 7-year-old children. The importance of this research is two-fold. First is knowledge acquisition--the potential to translate findings from animal experiments to the human condition. Second is public health importance-- optimizing maternal diet in early pregnancy could improve the health of the next generation.

描述（由研究者提供）：本申请涉及挑战区域08，“基因组学”和挑战主题08-AG-105（也称为OD [OBSSR] - 102），“研究关键发育期个体行为、社会和物理环境以及遗传/表观遗传过程之间相互作用的方法。“数十年的动物生理学实验明确表明，在发育的早期、可塑性、关键时期的扰动可能对慢性心脏代谢疾病的标志物（如肥胖、血压和葡萄糖耐受不良）以及寿命本身产生终身的、有时是不可逆的不利影响。表观遗传学领域最近揭示了这些观察结果背后的一些机制。例如，在黄色琼脂糖小鼠模型中，怀孕前后富含甲基供体的母体饮食会导致亚稳态表观等位基因的DNA甲基化，防止后代变得肥胖，糖尿病和癌症倾向。然而，还没有在人群中进行的研究，研究了从怀孕早期母体饮食到后代表型的表观遗传变化的途径。本研究的目的是研究妊娠早期母体饮食之间的关系，特别是甲基供体摄入量的变化，妊娠早期和晚期母体血液和脐带血中的总体DNA甲基化，以及3岁和7岁儿童的肥胖相关结局。我们将在特征良好的出生前队列研究Project Viva中开展该项目，该研究可能是唯一一项具有解决这些目标的设计特征的美国流行病学研究：前瞻性收集，验证，早期妊娠饮食信息，母体和脐带血标本，以及研究质量的后代心脏代谢表型数据。肥胖、心血管疾病、糖尿病和相关疾病是美国发病率和死亡率的主要原因，其最早的起源存在于胎儿期的行为和环境中。将表观遗传学数据添加到现有的流行病学研究中，可以将动物实验的知识转化为人类状况，并进行预防干预。考虑到潜在的科学和公共卫生影响，现在是时候大量涌入资金，以迅速推动这一领域的重大进展，而挑战赠款计划提供了正确的工具。 公共卫生关系：本研究的目标是检查妊娠早期母亲饮食对母体和胎儿DNA甲基化（一种表观遗传过程）的影响程度;以及DNA甲基化在多大程度上预测3岁和7岁儿童的肥胖和心血管危险因素。这项研究的重要性是双重的。首先是知识获取-将动物实验的发现转化为人类状况的潜力。其次是公共卫生的重要性-在怀孕早期优化产妇饮食可以改善下一代的健康。