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

美国男性和女性糖尿病患者中的新型脂肪因子和冠心病

基本信息

批准号：
8135032
负责人：
Qi Sun
金额：
$ 9.53万
依托单位：
HARVARD SCHOOL OF PUBLIC HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8135032
关键词：
Accounting Address Adipocytes Adipose tissue Alcohol consumption Animals Area Atherosclerosis Award Basic Science Biochemical Biological Assay Biological Markers Blood specimen Body Weight Body mass index Cardiovascular Diseases Case-Control Studies Cause of Death Cessation of life Clinical Clinical Medicine Cohort Studies Collection Communities Complication Coronary heart disease Data Development Diabetes Mellitus Dietary Factors Disease Disease Association Dyslipidemias Early Diagnosis Environment Environmental Risk Factor Epidemiologic Studies Epidemiology Etiology FABP4 gene Fatty acid glycerol esters Female Functional disorder Funding General Population Genetic Genetic Determinism Genome Goals Grant Health Professional Housing Human Hypertension Individual Inflammation Insulin Resistance K-Series Research Career Programs Knowledge Linkage Disequilibrium Measures Medical Mentored Clinical Scientist Development Award (K08)Mentors Methods Mission Molecular Epidemiology Molecular Genetics Molecular Weight National Heart, Lung, and Blood Institute Non-Insulin-Dependent Diabetes Mellitus Nurses&apos Health Study Outcome Pathway interactions Phase Physical activity Plasma Play Population Prevention Prevention strategy Preventive Medicine Public Health Schools Qi Randomized Regulation Research Research Activity Research Design Research Personnel Retinol Binding Proteins Risk Risk Factors Role Sampling Scientist Single Nucleotide Polymorphism Stroke Testing The Sun Training Training Activity Translating Translations Visceral Woman Work adipokines adiponectin atherogenesis base cardiovascular disorder risk cardiovascular risk factor career career development clinical practice cohort diabetic diabetic patient epidemiologic data experience follow-up gene environment interaction genetic analysis genetic epidemiology genetic risk factor genetic variant genome wide association study glycemic control heart disease prevention heart disease risk high risk human FABP4 protein human data indexing inflammatory marker interdisciplinary approach interest lifestyle factors men novel novel marker prospective public health relevance skills symposium therapeutic target treatment strategy waist circumference

项目摘要

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Coronary heart disease is an even stronger cause of death in diabetic patients than in the general population. As traditional CHD risk factors fail to explain all of the excess CHD risk among diabetic patients, identification of novel risk factors has become critical for disease treatment and prevention. Novel adipokines are promising candidates that are worth investigating in prospective human studies.

描述（由申请人提供）：迫切需要识别和检查可用于预防和治疗心血管疾病（CVD）的新型风险因素。 Qi Sun博士对CVD的新生物医学和遗传危险因素产生了浓厚的兴趣，并致力于CVD遗传和分子流行病学的职业。为了获得过渡到该领域独立研究人员所必需的知识和技能，Sun博士将实施一项全面的培训计划，包括遗传流行病学的高级课程工作，参加研讨会和研究会议，与导师的紧密互动以及该职业发展阶段的指导K99阶段的其他重要研究活动。博士。弗兰克·胡（Frank Hu）和詹姆斯·梅格斯（James Meigs）是两位成熟的研究人员和经验丰富的教练，将担任导师。哈佛大学公共卫生学院将为Sun博士的培训和职业发展提供理想的环境。哈佛医学界在各个领域拥有丰富的知名研究人员，他们将为Sun博士提供额外的培训。培训活动将着重于获取遗传流行病学方面的知识和技能，以及关于遗传数据的流行病学研究设计和统计分析的专业知识。这项培训对于Sun博士的发展是一名能够使用跨学科方法来解决分子和遗传CVD流行病学中的研究问题的独立科学家的必要和至关重要的。在该奖项的R00阶段期间，Sun博士提议分析和检查三种新颖的脂肪因子，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，在两种大型前瞻性群体中的2型糖尿病患者之间与冠状动脉疾病（CHD）有关。此外，Sun博士将进行全基因组关联（GWA）研究，以寻找这些生物标志物的遗传决定因素，并随后利用已鉴定的遗传变异来证实生物标志物 - 疾病蛋白酶酶的关联并检查基因环境的相互作用。这些生物标志物在动物研究中被鉴定出来，并被证明在冠心病病因中扮演因果关系。但是，缺乏前瞻性人数据限制了这些分子在人类治疗和预防CHD中的使用。遗传研究将大大加深对这些分子遗传调节的理解，并促进高危人群的鉴定。拟议的研究将提供及时和关键的数据，这些数据可以直接转化为CHD预防和治疗策略，因此与NHLBI的使命高度相关。公共卫生相关性：糖尿病患者的冠状动脉疾病比普通人群更强大。由于传统的CHD危险因素无法解释糖尿病患者中所有过量的CHD风险，因此对新型风险因素的识别对于疾病治疗和预防至关重要。新颖的脂肪因子是有希望的候选人，在前瞻性人类研究中值得研究。