Epigenetics and Nutrition: DNA Methylation, Dietary Intake and CVD

表观遗传学和营养:DNA 甲基化、膳食摄入和 CVD

基本信息

  • 批准号:
    8112344
  • 负责人:
  • 金额:
    $ 17.31万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-08-02 至 2013-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): It is widely accepted that diet and other lifestyle factors contribute significantly to the pathogenesis of cardiovascular disease, however the precise mechanisms for many of these factors remains poorly understood. Epigenetics refers to heritable changes in gene function that are not dependent on DNA sequence variation and includes the covalent modification of the DNA by methylation. Epigenetic factors provide a heritable, reversible and dynamic mechanism for regulating gene expression in response to the external stimuli induced by lifestyle/environment including nutrition. In this study we propose to explore epigenetic changes that occur in the progression to cardiovascular disease with a focus on dietary intake as the mediator in a well-characterized epidemiologic cohort of older adults, the Cardiovascular Health Study (CHS). Specifically, we will investigate: AIM 1: Is DNA methylation of specific loci associated with an increased risk of total mortality and, specifically, cardiovascular disease mortality, in older adults? AIM 2: Is DNA methylation of specific loci associated with an increased risk of incident cardiovascular disease, specifically myocardial infarction, angina pectoris, heart failure, and stroke? AIM 3: Is DNA methylation related to dietary intake prior to and after adjustment for other CVD risk factors such as hypertension and diabetes, subclinical disease, and behaviors/factors related to CVD risk? Are association independent or does methylation appears to be along the pathway to CVD? AIM 4: How are dietary factors related to epigenetic drift in persons with and without CVD? Does change in dietary intake correspond with change in DNA methylation? Does change in methylation mediate the association with CVD? We will measure DNA methylation in 30 pre-selected loci previously demonstrated to be related to CVD disease in stored blood samples of 500 CHS participants. To measure epigenetic drift, DNA methylation will be analyzed on blood samples taken 6 years apart to correspond with the food frequency questionnaires administered during CHS clinical evaluations. Disease outcomes will include total and cardiovascular mortality, incident myocardial infarction, angina pectoris, heart failure and stroke. Dietary data to be assessed will include estimated carbohydrate quality, including glycemix index, glycemic load, and cereal fiber intake; dietary saturated fat, linoleic acid, and oleic acid (energy-corrected); and weekly servings of whole grains, vegetables, fruits, meats, tuna/other fish, fried fish, and alcohol. Associations will be evaluated using Cox proportional hazards regression for incidence of CVD and mortality, and multiple linear regression and reduced rank regression for continuous measures of dietary intake. Models will be adjusted for other CVD risk factors to assess the role of diet in epigenetic drift and CVD. Results will lead to a better understanding of mechanisms controlling epigenomic variation allowing for identification of crucial disease-related alterations that may ultimately be targeted for novel treatment. PUBLIC HEALTH RELEVANCE: DNA methylation represents a gene regulatory mechanism affected by environmental exposures that may be implicated in complex diseases with both genetic and environmental components that are heritable. In this study we will investigate associations between DNA methylation and cardiovascular disease (CVD) with a focus on the role of dietary intake using data collected in the Cardiovascular Health Study (CHS) and conducting new analysis of stored DNA. By investigating associations between methylation in specific loci and nutrient intake, we can assess "epigenetic drift" and better understand the pathogenesis and mechanisms involved in the progression to CVD.
描述(由申请人提供):人们普遍认为饮食和其他生活方式因素对心血管疾病的发病有重要影响,但其中许多因素的确切机制仍然知之甚少。表观遗传学是指基因功能的可遗传变化,不依赖于DNA序列的变化,包括通过甲基化对DNA进行共价修饰。表观遗传因子为调控基因表达提供了一种可遗传的、可逆的和动态的机制,以响应包括营养在内的生活方式/环境所诱导的外部刺激。在这项研究中,我们建议探索心血管疾病进展过程中发生的表观遗传学变化,重点是饮食摄入量作为老年人流行病学队列的中介,心血管健康研究(CHS)。具体地说,我们将调查:目标1:特定基因座的DNA甲基化是否与老年人总死亡率,特别是心血管疾病死亡率的增加有关?目的2:特定基因座的DNA甲基化是否与心血管疾病,特别是心肌梗死、心绞痛、心力衰竭和中风的风险增加有关?目的3:DNA甲基化是否与其他心血管危险因素,如高血压和糖尿病、亚临床疾病以及与心血管危险相关的行为/因素调整前后的饮食摄入量有关?甲基化是否独立于关联,或者甲基化似乎是沿着CVD的途径?目的4:饮食因素与有和没有心血管疾病患者的表观遗传漂移有什么关系?饮食摄入量的变化是否与DNA甲基化的变化相对应?甲基化的改变是否介导了与心血管疾病的关联?我们将在500名CHS参与者的储存血液样本中测量先前被证明与心血管疾病相关的30个预先选择的基因座的DNA甲基化。为了测量表观遗传漂移,将对相隔6年的血液样本进行DNA甲基化分析,以与在CHS临床评估期间发放的食物频率问卷相对应。疾病结果将包括总死亡率和心血管死亡率、突发心肌梗死、心绞痛、心力衰竭和中风。要评估的饮食数据将包括估计的碳水化合物质量,包括血糖指数、血糖负荷和谷类纤维摄入量;膳食饱和脂肪、亚油酸和油酸(能量校正);以及每周全谷物、蔬菜、水果、肉类、金枪鱼/其他鱼、炸鱼和酒精的供应量。将使用COX比例风险回归对心血管疾病的发生率和死亡率进行评估,并使用多元线性回归和降阶回归对饮食摄入量的连续测量进行评估。模型将针对其他心血管疾病危险因素进行调整,以评估饮食在表观遗传漂移和心血管疾病中的作用。结果将导致更好地理解控制表观基因组变异的机制,从而识别最终可能成为新治疗目标的关键疾病相关改变。 与公共卫生相关:DNA甲基化是一种受环境暴露影响的基因调控机制,可能与具有遗传和环境成分的复杂疾病有关,这些成分都是可遗传的。在这项研究中,我们将利用心血管健康研究(CHS)收集的数据和对储存的DNA进行新的分析,研究DNA甲基化与心血管疾病(CVD)之间的关系,重点是饮食摄入的作用。通过研究特定基因座甲基化与营养摄入之间的关系,我们可以评估表观遗传漂移,并更好地理解CVD的发病机制和进展机制。

项目成果

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ANNETTE L. FITZPATRICK其他文献

ANNETTE L. FITZPATRICK的其他文献

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{{ truncateString('ANNETTE L. FITZPATRICK', 18)}}的其他基金

Building Capacity to Address the Burden of Cardiometabolic Risk Factors and Diseases in LMICs
建设能力以解决中低收入国家心脏代谢危险因素和疾病的负担
  • 批准号:
    10634663
  • 财政年份:
    2020
  • 资助金额:
    $ 17.31万
  • 项目类别:
Building Capacity to Address the Burden of Cardiometabolic Risk Factors and Diseases in LMICs
建设能力以解决中低收入国家心脏代谢危险因素和疾病的负担
  • 批准号:
    10054300
  • 财政年份:
    2020
  • 资助金额:
    $ 17.31万
  • 项目类别:
Building Capacity to Address the Burden of Cardiometabolic Risk Factors and Diseases in LMICs
建设能力以解决中低收入国家心脏代谢危险因素和疾病的负担
  • 批准号:
    10256077
  • 财政年份:
    2020
  • 资助金额:
    $ 17.31万
  • 项目类别:
Building Capacity to Address the Burden of Cardiometabolic Risk Factors and Diseases in LMICs
建设能力以解决中低收入国家心脏代谢危险因素和疾病的负担
  • 批准号:
    10435535
  • 财政年份:
    2020
  • 资助金额:
    $ 17.31万
  • 项目类别:
Air pollution, the social environment, and Alzheimer's disease: Risk and resilience in the Ginkgo Evaluation Memory Study
空气污染、社会环境和阿尔茨海默病:银杏评估记忆研究中的风险和恢复力
  • 批准号:
    9392093
  • 财政年份:
    2017
  • 资助金额:
    $ 17.31万
  • 项目类别:
Domains of Inflammation and Risk of Dementia
炎症领域和痴呆症风险
  • 批准号:
    8022041
  • 财政年份:
    2011
  • 资助金额:
    $ 17.31万
  • 项目类别:
Domains of Inflammation and Risk of Dementia
炎症领域和痴呆症风险
  • 批准号:
    8217093
  • 财政年份:
    2011
  • 资助金额:
    $ 17.31万
  • 项目类别:
Domains of Inflammation and Risk of Dementia
炎症领域和痴呆症风险
  • 批准号:
    8433263
  • 财政年份:
    2011
  • 资助金额:
    $ 17.31万
  • 项目类别:
Epigenetics and Nutrition: DNA Methylation, Dietary Intake and CVD
表观遗传学和营养:DNA 甲基化、膳食摄入和 CVD
  • 批准号:
    8310940
  • 财政年份:
    2011
  • 资助金额:
    $ 17.31万
  • 项目类别:
Neurologic manifestations of cerebrovascular disease in Da Nang, Viet Nam
越南岘港脑血管疾病的神经系统表现
  • 批准号:
    7845622
  • 财政年份:
    2009
  • 资助金额:
    $ 17.31万
  • 项目类别:

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