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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）的新风险因素。孙奇博士对识别CVD的新型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生涯。为了获得过渡为该领域独立研究员所需的知识和技能，孙博士将实施全面的培训计划，包括遗传流行病学的高级课程、参加研讨会和研究会议、与导师的密切互动以及职业发展奖指导的K99阶段的其他重要研究活动。博士。两位知名研究人员和经验丰富的培训师 Frank Hu 和 James Meigs 将担任导师。哈佛大学公共卫生学院将为孙博士的培训和职业发展提供理想的环境。哈佛医学界拥有众多在各个领域具有专业知识的资深研究人员，他们将为孙博士提供额外的培训。培训活动将侧重于获取遗传流行病学知识和技能，以及流行病学研究设计和遗传数据统计分析的专业知识。这种培训对于孙博士发展成为一名能够利用跨学科方法解决分子和遗传CVD流行病学研究问题的独立科学家来说是必要且必不可少的。在该奖项的R00阶段，孙博士建议在两个大型前瞻性队列中测定和检查血浆中与2型糖尿病患者冠心病（CHD）相关的三种新型脂肪因子，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。此外，孙博士还将开展全基因组关联（GWA）研究，寻找这些生物标志物的遗传决定因素，随后利用已识别的遗传变异来证实生物标志物与疾病的关联，并检查基因与环境的相互作用。这些生物标志物在动物研究中得到鉴定，并被证明在 CHD 的病因学中发挥因果作用。然而，缺乏前瞻性人类数据限制了这些分子在治疗和预防人类冠心病方面的使用。遗传学研究将极大地加深对这些分子的遗传调控的理解，并有助于识别高危人群。拟议的研究将提供及时和关键的数据，可直接转化为 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：冠心病是糖尿病患者比一般人群更严重的死亡原因。由于传统的冠心病危险因素无法解释糖尿病患者中所有过高的冠心病风险，因此识别新的危险因素对于疾病治疗和预防至关重要。新型脂肪因子是有前途的候选者，值得在前瞻性人类研究中进行研究。