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（由适用提供）：最常见的童年慢性疾病之一的1型糖尿病（T1D）的事件正在增加，这可能是由于受保护因素的减少所致。虽然已经假设维生素D和Omega-3脂肪酸是T1D的饮食因素，但支持其作用的证据要么矛盾或缺乏。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和不准确的，因此很难理解饮食在疾病发展中的作用。存在着通过代谢组学分析独立评估饮食摄入的迫切需要，并为可靠的预测指标与疾病过程的病因联系起来。代谢组分析可以用作体内饮食摄入和代谢的独立标志。 T1D是一种复杂的慢性疾病，具有多种遗传和环境风险因素，影响了疾病自然史的关键时间。因此，有必要将前瞻性收集的饮食数据与饮食生物标志物，代谢产物，遗传变异，DNA甲基化和基因表达数据相结合，以便更充分了解所涉及的途径。例如，尚不清楚欧米茄3脂肪酸和维生素D是否与遗传变异（营养材料）相互作用，还是通过表观遗传学变化（Nutrigenomics）来改变基因表达，以降低胰岛自身免疫性（IA）的风险，即临床阶段，即临床前阶段，该阶段是T1D和T1D本身。在T1D风险增加的2,547名儿童的年轻（Daisy）队列中，糖尿病自身免疫研究在阐明IA和T1D的营养病因学方面取得了重大进展，尽管这突显了关联流行病学工具的关系和局限性的复杂性。我们建议使用雏菊中前瞻性收集的数据进行嵌套的病例对照研究。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，以及使用尖端的代谢组学，营养和营养学技术的IA和T1D风险。我们建议通过补充维生素D结合蛋白（以计算免费的25 [OH] D），以及与维生素D和omega-3脂肪酸途径相关的代谢物，以获取INTAKE和营养独立的，独立于自然，可以进一步探索T1D的营养流行病学（为了计算与维生素D和omega-3脂肪酸途径相关的代谢物，以获取intake和营养不良，独立于自然的含量。然后，我们将通过研究维生素D和omega-3脂肪酸对IA和T1D的影响是否因遗传变异而差异，从而探索T1D的营养学。最后，我们将通过研究维生素D和Omega-3脂肪酸摄入量是否通过表观遗传变化来影响T1D的脂肪酸摄入量是否会影响T1D的易感性来探索T1D的营养学。在理解维生素D和omega-3脂肪酸与IA和T1D的发展之间的生物学机制方面存在很大的差距。阐明这些机制对于旨在减少T1D燃烧的预防和治疗策略的发展至关重要。