Novel Adipokines and Coronary Heart Disease in U.S. Men and Women with Diabetes

6.项目概要/摘要 迫切需要确定和审查新的风险因素，可用于预防和 治疗心血管疾病（CVD）。孙奇博士对鉴定新的 生物医学和遗传风险因素的心血管疾病，并致力于职业生涯中的遗传和分子 CVD的流行病学。获得必要的知识和技能过渡到一个独立的 作为这一领域的研究人员，孙博士将实施一个全面的培训计划，包括高级课程 从事遗传流行病学工作，出席研讨会和研究会议，与 导师，和其他重要的研究活动，在辅导K99阶段的职业发展奖。 Drs. Frank Hu和James Meigs，两位知名的研究人员和经验丰富的培训师，将担任 作为导师。哈佛公共卫生学院将为孙博士的培训提供理想的环境 和职业发展。哈佛医学界聚集了一批经验丰富的研究人员 他们将为孙博士提供额外的培训。培训活动将侧重于 获得遗传流行病学的知识和技能，以及流行病学研究设计的专业知识 和遗传数据的统计分析。这种训练是必要的和必不可少的孙博士的发展， 一个独立的科学家能够使用跨学科的方法来解决研究问题， 分子和遗传CVD流行病学。 在该奖项的R 00阶段，孙博士建议分析和检查三种新的脂肪因子，即， 视黄醇结合蛋白4、脂肪酸结合蛋白4和高分子量脂联素， 在两个大型前瞻性队列中，2型糖尿病患者与冠心病（CHD）的关系。在 此外，孙博士将进行全基因组关联（GWA）研究，以寻找遗传决定因素， 这些生物标志物并随后利用鉴定的遗传变异来证实生物标志物疾病 研究基因与环境的相互作用。这些生物标志物是在动物研究中确定的 并被证明在冠心病的病因学中起着因果作用。然而，由于缺乏前瞻性的人类数据， 这些分子在治疗和预防人类CHD中的应用。基因研究将大大深化 了解这些分子的遗传调控，并促进高风险的识别 人口。拟议的研究将提供可直接转化为CHD的及时和关键数据 预防和治疗策略，因此，与国家HLBI的使命高度相关。

6. Project Summary/Abstract There is an urgent need to identify and examine novel risk factors that can be utilized in the prevention and treatment of cardiovascular disease (CVD). Dr. Qi Sun has developed a strong interest in identifying novel biomedical and genetic risk factors for CVD and dedicated himself to a career in genetic and molecular epidemiology of CVD. To gain knowledge and skills necessary for the transition into an independent researcher in this field, Dr. Sun will implement a comprehensive training plan encompassing advanced course work in genetic epidemiology, attendance at seminars and research conferences, close interactions with mentors, and other significant research activities in the mentored K99 phase of this career development award. Drs. Frank Hu and James Meigs, two well-established researchers and highly experienced trainers, will serve as the mentors. The Harvard School of Public Health will provide an ideal environment for Dr. Sun's training and career development. The Harvard medical community houses a rich collection of established investigators with expertise in various areas who will provide additional training to Dr. Sun. The training activities will focus on acquiring knowledge and skills in genetic epidemiology, as well as expertise on epidemiologic study design and statistical analysis of genetic data. This training is necessary and essential for Dr. Sun's development into an independent scientist capable of using interdisciplinary approaches to addressing research questions in molecular and genetic CVD epidemiology. During the R00 phase of this award, Dr. Sun proposes to assay and examine three novel adipokines, i.e., retinol binding protein 4, fatty acid binding protein 4, and high-molecular-weight adiponectin, in plasma in relation to coronary heart disease (CHD) among type 2 diabetic patients in two large prospective cohorts. In addition, Dr. Sun will conduct whole-genome association (GWA) studies to search for genetic determinants for these biomarkers and subsequently utilize identified genetic variants to corroborate biomarker-disease associations and to examine gene-environment interactions. These biomarkers are identified in animal studies and proven to play causal roles in the etiology of CHD. However, lack of prospective human data limits the use of these molecules in the treatment and prevention of CHD in humans. The genetic studies will greatly deepen the understanding of genetic regulation on these molecules and facilitate the identification of high-risk populations. The proposed studies will provide timely and critical data that can be directly translated into CHD prevention and treatment strategies and, thus, are highly relevant to the mission of NHLBI.