Magnesium Intake, Gene Variants, and Type 2 Diabetes

描述（由申请人提供）： 拟定PI Yiqing Song博士的长期目标是在流行病学研究中研究营养代谢、遗传变异、代谢生物标志物和2型糖尿病（DM）风险之间的相互关系。通过与布里格姆妇女医院的导师合作，PI将发展该项目所需的人口遗传学研究各个方面的专业知识，包括遗传统计学和生物信息学。镁是一种必需的营养素，摄入足够的镁对维持人体胰岛素和葡萄糖的稳态很重要。也有越来越多的证据，主要来自实验研究，镁的吸收和运输的遗传基础。这个研究项目有两个主要目标。首先，本研究将扩展申请人之前的流行病学研究，以检查女性健康研究（WHS）中镁摄入量与全身炎症生物标志物以及脂质和脂蛋白代谢之间的相互关系，WHS是一项大型前瞻性队列研究，包含存档的生物标本以及生活方式因素和一些生化标志物的详细信息。其次，拟议的遗传学研究将在两个大型队列的两项前瞻性病例对照研究中检查参与镁稳态途径的七个基因中的常见遗传变异与2型糖尿病风险的关系，WHS（600例2型糖尿病病例和600例匹配对照）和卫生专业人员随访研究（HPFS）队列（1000例病例和1000例对照）。除了主要目标外，拟议的研究将评估镁摄入量是否与这些遗传变异相互作用以改变2型糖尿病的风险，并将应用几种探索性分析方法来探索2型糖尿病风险的复杂基因-基因和基因-环境相互作用。该提案将使PI能够发展技能，以开展其作为糖尿病流行病学独立研究者的职业生涯。拟议的研究项目将提供一种独特而全面的方法，以更好地了解镁稳态在糖尿病病因学中的作用机制，帮助识别高风险个体，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.