Magnesium Intake, Gene Variants, and Type 2 Diabetes

描述(由申请人提供)： 拟议的PI宋一青博士的长期目标是在流行病学研究中调查营养代谢、遗传变异、代谢生物标记物和2型糖尿病(DM)风险之间的相互关系。通过与他在Brigham和妇女医院的导师合作，PI将在这个项目所需的人口遗传学研究的所有方面发展专业知识，包括遗传统计和生物信息学。摄入足够的镁是一种基本的营养物质，对维持人体内胰岛素和葡萄糖的动态平衡非常重要。也有越来越多的证据，主要来自实验研究，证明镁的吸收和运输具有遗传基础。这项拟议的研究项目将有两个主要目标。首先，这项研究将扩展申请人之前的流行病学研究，以在妇女健康研究(WHS)中检查镁摄入量与全身炎症生物标记物和脂类和脂蛋白代谢生物标记物之间的相互关系，这是一个拥有存档生物样本和生活方式因素和一些生化标记物的详细信息的大型前瞻性队列。其次，拟议的遗传学研究将在两个大型队列中嵌套的两个前瞻性病例对照研究中，检查镁稳态途径中涉及的七个基因的常见基因变异与2型糖尿病风险的关系，这两个队列是WHS(600例2型糖尿病病例和600名匹配对照)和卫生专业人员后续研究(HPFS)队列(1000例病例和1000名匹配对照)。除了主要目标外，这项拟议的研究还将评估镁摄入量是否与这些遗传变异相互作用来改变2型糖尿病的风险，并将应用几种探索性分析方法来探索复杂的基因-基因和基因-环境相互作用对2型糖尿病风险的影响。这项建议将使PI能够发展技能，开始他作为一名专注于糖尿病流行病学的独立调查员的职业生涯。拟议的研究项目将提供一种独特和全面的方法，以更好地了解镁稳态在糖尿病病因学中的作用机制，帮助识别高危个体，并提出新的和更个性化的治疗和/或预防策略。

DESCRIPTION (provided by applicant): The long-term goal of the proposed PI, Dr. Yiqing Song, is to investigate the interrelationships among nutrient metabolisms, genetic variants, metabolic biomarkers, and risk of type 2 diabetes mellitus (DM) in epidemiologic studies. Through collaboration with his mentors at Brigham and Women's Hospital, the PI will develop expertise in all aspects of population genetic research needed for this project including genetic statistics and bioinformatics. Adequate intake of magnesium, an essential nutrient, is important in maintaining insulin and glucose homeostasis in the human body. There is also growing evidence, mostly from experimental studies, for a genetic basis of magnesium absorption and transport. This proposed research project will have two primary goals. First, this study will extend the applicant's previous epidemiologic research to examine the interrelationships between magnesium intake and biomarkers of systemic inflammation and lipid and lipoprotein metabolism in the Women's Health Study (WHS), a large prospective cohort with archived bio-specimens and detailed information on lifestyle factors and some biochemical markers. Second, the proposed genetic research will examine common genetic variants in seven genes involved in the magnesium homeostasis pathway in relation to the risk of type 2 DM in two prospective case-control studies nested in two large cohorts, the WHS (600 incident type 2 DM cases and 600 matched controls) and the Health Professionals Follow-up Study (HPFS) cohorts (1000 cases and 1000 matched controls). In addition to the primary goals, the proposed study will assess whether magnesium intake interacts with these genetic variants to modify risk of type 2 DM and will also apply several exploratory analytic approaches to explore the complex gene-gene and gene-environment interactions on type 2 DM risk. This proposal will enable the PI to develop the skills to launch his career as an independent investigator focusing on diabetes epidemiology. The proposed research project will provide a unique and comprehensive approach to better understand the mechanisms underlying the role of magnesium homeostasis in diabetes etiology, to help identify high-risk individuals, and to suggest new and more individualized treatment and/or prevention strategies.