Diet and Gene Interactions and the Risk of Type 2 Diabetes

描述(由申请人提供)： 这个K0I应用程序是为了支持新的研究人员的职业发展，以获得在糖尿病病因学方面进行多学科研究的知识和技能。在美国和许多其他国家，2型糖尿病(T2D)是发病率和死亡率的主要原因。饮食摄入量在T2D的病因中起着重要作用。然而，证据并不一致，特别是关于保护性饮食因素，如omega 3脂肪酸、异黄酮类和抗氧化剂。结果不一致的一个原因可能是未能考虑个体宿主对饮食摄入的反应。累积的证据表明，基因-饮食相互作用在T2D的病因中起着重要作用。来自实验室研究的数据表明，豆类和豆制品中丰富的异黄酮类和鱼油中丰富的二十碳五烯酸可以激活PPAR基因的表达。在观察性和干预性研究中，体力活动是T2D的保护因素，在T2D的发展过程中已被证明与PPAR和PGC1基因相互作用。在K01的应用中，候选人建议研究PPAR和PGC1基因的作用以及它们与饮食摄入量和体力活动对糖尿病风险的相互作用。这两个相关的基因家族之所以被选中，是因为它们在能量平衡和胰岛素抵抗方面发挥着重要作用。来自正在进行的880例T2D病例和1500名对照的全基因组关联研究(GWAS)的数据将被用于筛选有前景的SNPs。重复研究将使用1500例T2D病例和1500例匹配对照的独立集合进行。基因-饮食和基因-体力活动的相互作用将在筛选和复制阶段参与者的组合中进行评估。从研究中获得的知识将对T2D的预防和个体化治疗产生重大的公共卫生影响。同样重要的是，通过这个奖项和研究申请，候选人将在进行分子流行病学研究方面获得新的知识和技能，这将有助于她实现她的职业目标，即成为T2D的独立研究人员。

DESCRIPTION (provided by applicant): This K0I application is to support career development for a new investigator to gain knowledge and skills in conducting multi-disciplinary research on diabetes etiology. Type 2 diabetes (T2D) is a major cause of morbidity and mortality in the United States and many other countries. Dietary intake has been suggested to play an important role in the etiology of T2D. However, the evidence is inconsistent, particularly regarding protective dietary factors, such as omega 3 fatty acids, isoflavones and antioxidants. A reason for inconsistencies in results may be due to the failure to consider individual host response to dietary intake. Cumulative evidence has suggested an important role of gene-diet interaction in the etiology of T2D. Data from laboratory studies have suggested that isoflavones, abundant in legumes and soy products, and eicosapentaenoic acid, abundant in fish oils, activate PPAR gene expression. Physical activity, a protective factor for T2D, has been shown to interact with PPAR and PGC1 genes in the development of T2D in observational and intervention studies. In this K01 application, the candidate proposes to investigate the role of PPAR and PGC1 genes and their interaction with dietary intake and physical activity on diabetes risk. These two related families of genes were selected because of their important role on energy balance and insulin resistance. Data from an on-going genome wide association study (GWAS) of 880 T2D cases and 1500 controls will be used to screen promising SNPs. A replication study will be performed using an independent set of 1500 T2D cases and 1500 matched controls. Gene-diet and gene-physical activity interactions will be evaluated in a combined set of screening and replication phase participants. The knowledge gained from the study will have a significant public health impact on prevention and individualized treatment of T2D. Of equal importance, through this award and research application, the candidate will gain new knowledge and skills in conducting molecular epidemiological study that will facilitate her achieving her career goals, i.e., to become an independent researcher in T2D.