Magnesium Intake, Gene Variants, and Type 2 Diabetes

镁摄入量、基因变异和 2 型糖尿病

• 批准号: 7595790
• 负责人: Yiqing Song
• 金额: $ 13.64万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7595790
• 关键词: Age; Alcohol consumption; Apolipoprotein A-I; Archives; Biochemical Markers; Bioinformatics; Biological Markers; Body mass index; C-reactive protein; Candidate Disease Gene; Cholesterol; Chronic; Coffee; Cohort Studies; Collaborations; Complex; Diabetes Mellitus; Dyslipidemias; Epidemiologic Studies; Epidemiology; Etiology; Family; Family history of; Fibrinogen; Follow-Up Studies; Genes; Genetic; Genetic Research; Genetic Variation; Genotype; Glycosylated hemoglobin A; Goals; Health Professional; High Density Lipoprotein Cholesterol; Homeostasis; Hospitals; Human; Human body; Hypomagnesemia; Individual; Inflammation; Inflammatory; Insulin; Intake; Intercellular adhesion molecule 1; Interleukin-6; Intestines; Ion Channel; Kidney; LDL Cholesterol Lipoproteins; Lipids; Lipoprotein (a); Lipoproteins; Magnesium; Membrane Potentials; Mentors; Metabolic; Metabolism; Mitochondria; Na(+)-K(+)-Exchanging ATPase; Nested Case-Control Study; Non-Insulin-Dependent Diabetes Mellitus; Nutrient; Pathway interactions; Physical activity; Plasma; Population Genetics; Predisposition; Prevention strategy; RNA Splicing; Research Personnel; Research Project Grants; Risk; Risk Factors; Role; Single Nucleotide Polymorphism; Sodium Chloride; Specimen; Testing; Triglycerides; Woman; Women' s Health; absorption; base; blood glucose regulation; career; cigarette smoking; cohort; diabetes risk; gene environment interaction; genetic association; genetic variant; high risk; lifestyle factors; lipid metabolism; member; novel; nutrient metabolism; prospective; receptor; research study; skills; solute; statistics; symporter

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.

描述（由申请人提供）： 拟议 PI 宋一庆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、代谢生物标志物和 2 型糖尿病 (DM) 风险之间的相互关系。通过与布莱根妇女医院的导师合作，首席研究员将开发该项目所需的群体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。摄入充足的镁是一种必需营养素，对于维持人体内胰岛素和葡萄糖稳态非常重要。还有越来越多的证据（主要来自实验研究）表明镁吸收和运输的遗传基础。该拟议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，以检查女性健康研究（WHS）中镁摄入量与全身炎症和脂质和脂蛋白代谢生物标志物之间的相互关系，这是一个大型前瞻性队列，包含存档的生物样本以及生活方式因素和一些生化标志物的详细信息。其次，拟议的基因研究将在两个大型队列（WHS（600 例 2 型糖尿病病例和 600 例匹配对照）和健康专业人员随访研究 (HPFS) 队列（1000 例病例和 1000 例匹配对照））中的两项前瞻性病例对照研究中，检查参与镁稳态途径的 7 个基因的常见遗传变异与 2 型糖尿病风险的关系。除了主要目标外，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。该提案将使 PI 能够发展技能，以开展其作为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、更个性化的治疗和/或预防策略。