Nutrigenetics & -genomics of Vitamin D and Omega-3 Fatty Acids in Type 1 Diabetes

营养遗传学

• 批准号: 9119814
• 负责人: JILL M NORRIS
• 金额: $ 67.63万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9119814
• 关键词: Adolescent; Affect; Autoimmunity; Biological Markers; Child; Childhood; Chronic Disease; Complex; DNA Methylation; Data; Development; Diabetes Mellitus; Diet; Dietary Factors; Dietary intake; Disease; Environmental Risk Factor; Epidemiologic Studies; Epidemiology; Epigenetic Process; Etiology; Gene Expression; Genes; Genetic Risk; Genetic Variation; Genomics; Health; Incidence; Insulin-Dependent Diabetes Mellitus; Intake; Investigation; Mediating; Metabolism; Nature; Nested Case-Control Study; Nutritional; Omega-3 Fatty Acids; Pathway interactions; Patient Self-Report; Phase; Physicians; Positioning Attribute; Practice Guidelines; Predisposition; Prevention strategy; Process; Recording of previous events; Risk; Role; Techniques; Time; Translating; Variant; Vitamin D; Vitamin D-Binding Protein; cohort; diabetes risk; disease natural history; endocrine pancreas development; epidemiology study; epigenomics; genetic variant; islet; metabolomics; nutrient metabolism; nutrition; nutrition related genetics; nutritional genomics; pre-clinical; study population; tool; treatment strategy

 DESCRIPTION (provided by applicant): The incidence of type 1 diabetes (T1D), one of the most common chronic diseases of childhood, is increasing, perhaps due to decreases in protective factors. While vitamin D and omega-3 fatty acids have been hypothesized to be protective dietary factors for T1D, the evidence supporting their role is either contradictory or lacking. Many nutrition epidemiology studies rely on self-reported dietary intake information, which can be subjective and inaccurate, making it difficult to understand the role of diet in disease development. There exists a critical need for independent assessment of dietary intake via metabolomics profiling and for reliable predictors that connect nutrient metabolism with the etiology of the disease process. Metabolomic profiling can be used as an independent marker of dietary intake and metabolism within the body. T1D is a complex chronic disease, with multiple genetic and environmental risk factors influencing critical time-points in the disease's natural history; therefore, it is necessary to combine prospectively-collected dietary data with dietary biomarkers, metabolites, genetic variants, DNA methylation and gene expression data in order to more fully understand the pathways involved. For example, it is not known whether omega-3 fatty acids and vitamin D interact with genetic variants (nutrigenetics), or whether they alter gene expression, via epigenomic changes (nutrigenomics), to reduce risk for islet autoimmunity (IA), the pre-clinical phase that precedes T1D, and T1D itself. The Diabetes Autoimmunity Study in the Young (DAISY) cohort of 2,547 children at increased T1D risk has made substantial progress in elucidating the nutritional etiology of IA and T1D, although this has highlighted the complexities of the relationships and limitations of the tools of associational epidemiology. We propose to conduct a nested case-control study using the prospectively collected data in DAISY. The overall aim of the study is to elucidate the nutrition epidemiological findings regarding vitamin D and omega-3 fatty acids and risk of IA and T1D using cutting-edge metabolomics, nutrigenetic and nutrigenomics techniques. We propose to further explore the nutrition epidemiology of T1D by supplementing existing nutrition and biomarker data with vitamin D binding protein (in order to calculate free 25[OH]D), and metabolites related to vitamin D and omega-3 fatty acid pathways, in order to obtain an assessment of intake and nutrient metabolism, independent of self-reported intake. We will then explore the nutrigenetics of T1D by examining whether the effect of vitamin D and omega-3 fatty acids on IA and T1D differs by genetic variation. Finally, we will explore the nutrigenomics of T1D by investigating whether vitamin D and omega-3 fatty acid intake alter gene expression, via epigenetic changes, to influence predisposition to T1D. There are significant gaps in understanding the biologic mechanisms underlying the association between vitamin D and omega-3 fatty acids and the development of IA and T1D. Elucidating these mechanisms is critical for the development of prevention and treatment strategies aimed at reducing the burden of T1D.

 描述（由申请人提供）：1 型糖尿病 (T1D) 是儿童最常见的慢性疾病之一，其发病率正在增加，这可能是由于保护因素的减少，而维生素 D 和 omega-3 脂肪酸却被忽视了。尽管饮食因素是 T1D 的保护性因素，但支持其作用的证据要么相互矛盾，要么缺乏。许多营养流行病学研究依赖于自我报告的饮食摄入信息，这些信息可能是主观且不准确的，因此很难理解饮食的作用。迫切需要通过代谢组学分析对饮食摄入量进行独立评估，以及将营养代谢与疾病过程的病因学联系起来的可靠预测因子，可用作饮食摄入和代谢的独立标记。 T1D 是一种复杂的慢性疾病，有多种遗传和环境风险因素影响疾病自然史的关键时间点，因此，有必要将前瞻性收集的饮食数据与饮食生物标志物、代谢物结合起来。例如，尚不清楚 omega-3 脂肪酸和维生素 D 是否与遗传变异（营养遗传学）相互作用，或者它们是否改变基因遗传表达。通过表观基因组变化（营养基因组学），降低胰岛自身免疫 (IA)、T1D 之前的临床前阶段以及年轻糖尿病自身免疫研究的风险。 （DAISY）由 2,547 名 T1D 风险增加的儿童组成的队列在阐明 IA 和 T1D 的营养病因方面取得了实质性进展，尽管这凸显了关联流行病学工具的复杂性和局限性，我们建议进行嵌套病例。 - 使用 DAISY 中前瞻性收集的数据进行对照研究 该研究的总体目的是阐明有关维生素 D 和 omega-3 脂肪酸的营养流行病学发现。我们建议通过使用维生素 D 结合蛋白补充现有的营养和生物标志物数据（以便计算游离 25[OH]D），进一步探索 T1D 的营养流行病学。 ，以及与维生素 D 和 omega-3 脂肪酸途径相关的代谢物，以便获得独立于自我报告摄入量的摄入量和营养代谢的评估。通过检查维生素 D 和 omega-3 脂肪酸对 IA 和 T1D 的影响是否因遗传变异而有所不同，来研究 T1D 的营养遗传学。最后，我们将通过研究维生素 D 和 omega-3 脂肪酸的摄入是否会改变基因表达来探索 T1D 的营养基因组学。通过表观遗传变化影响 T1D 的易感性 对于维生素 D 和 omega-3 脂肪酸与 IA 和 IA 发展之间关联的生物学机制的理解存在显着差距。阐明这些机制对于制定旨在减轻 T1D 负担的预防和治疗策略至关重要。