Ghrelin, PAil and Their Associations with Adipokine

Ghrelin、PAil 及其与脂肪因子的关联

• 批准号: 8552058
• 负责人: Sarah Buxbaum
• 金额: $ 8.09万
• 依托单位: JACKSON STATE UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8552058
• 关键词: Adipose tissue; Admixture; African American; Age; Biological Assay; Biological Markers; Body Composition; Calcium; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Cohort Studies; Computer software; Confounding Factors (Epidemiology); Consent; Coronary; DNA; Data; Development; Eating; Energy Intake; Epidemic; Family history of; Genes; Genetic; Genetic Polymorphism; Genotype; Haplotypes; Heart; Heart Diseases; Heritability; Homeostasis; Human; Hydrogen Peroxide; Hypertension; Hypothalamic structure; Image; Individual; Institutes; Insulin Resistance; Leptin; Longitudinal Studies; Measures; Metabolic; Metabolic syndrome; Metabolism; Methods; Modeling; Multivariate Analysis; National Center on Minority Health and Health Disparities; Non-Insulin-Dependent Diabetes Mellitus; Normal Statistical Distribution; Normalcy; Obesity; Participant; Physiology; Plasma; Plasminogen Activator Inhibitor 1; Play; Predictive Factor; Primary Health Care; Procedures; Provider; Regression Analysis; Research Personnel; Risk Factors; Role; Side; Spearman Rank Correlation Coefficient; Testing; Thick; Time; Variant; Visceral; Waist-Hip Ratio; X-Ray Computed Tomography; adiponectin; base; cohort; exome sequencing; fasting glucose; genetic risk factor; genome wide association study; genome-wide; ghrelin; health disparity; intima media; obesity risk; peptide hormone; programs; sex; statistics; subcutaneous; tau Proteins; waist circumference

This submission responds to the RFA for an Exploratory NCMHD Center for Excellence (RFA-MD-08- 0049). We propose to examine the distributions of two biomarkers in a large, ongoing, well-characterized longitudinal study of African Americans, the Jackson Heart Study, and to characterize their association with a number of known risk factors for metabolic syndrome (MetS), type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD), with a long-term aim of identifying more precisely the plasma levels that would alert a primary care provider to those who are most likely to benefit from treatment. We will assess the relevance of family history by estimating familial correlations and the heritability. In addition to examining plasma levels of ghrelin and PAI-1, we wish to examine them in the context of other risk factors, including obesity and genetic risk factors in GWAS analyses. Specifically, this study aims to describe the distribution of plasma levels of ghrelin and PAI-1 and their heritability in the Jackson Heart Study (JHS) cohort, examine environmental and genetic correlations between plasma ghrelin and PAI-1 levels and factors predictive of heart disease in the JHS cohort, and find polymorphisms and haplotypes associated with plasma ghrelin and PAI-1 levels in the JHS. Because ghrelin plays a significant role in energy homeostasis via the hypothalamus by controlling food intake, and is a powerful orexigenic and adipogenic agent in human physiology, it is important to study this biomarker in a cohort at the epicenter of the obesity epidemic. Ghrelin's effect on metabolism is thought to be the opposite of leptin's, and these two peptide hormones may act synergistically to increase insulin resistance and metabolic abnormalities \ Leptin was assayed in the JHS exam 1. We propose to assay both ghrelin and leptin in exam 3, and to assay ghrelin in exam 1. Analysis of exam 1 biomarker data in conjunction with measures of obesity in exam 3, such as BMI, waist circumference, hip to waist ratio, as well as imaging data providing measures of visceral and subcutaneous adiposity and their ratio, will allow us to determine if the biomarkers play a predictive role in the development of obesity.

本提交文件是对探索性NCMHD卓越中心RFA（RFA-MD-08- 0049）。我们建议在一个大的，正在进行的，充分表征的 非裔美国人的纵向研究，杰克逊心脏研究，并描述他们与 代谢综合征（MetS）、2型糖尿病（T2 D）和 心血管疾病（CVD），长期目标是更精确地确定血浆水平， 会提醒初级保健提供者注意那些最有可能从治疗中受益的人。我们将评估 通过估计家族相关性和遗传度来估计家族史的相关性。除了审查 血浆ghrelin和派-1水平，我们希望在其他危险因素的背景下检查它们，包括 肥胖和遗传风险因素的GWAS分析。 具体地说，本研究的目的是描述血浆ghrelin和派-1水平的分布及其与糖尿病的关系。 在杰克逊心脏研究（JHS）队列中的遗传率，检查环境和遗传相关性 血浆ghrelin和派-1水平与JHS队列中心脏病的预测因素之间的关系，并发现 与JHS患者血浆ghrelin和派-1水平相关的多态性和单倍型。 因为ghrelin通过下丘脑控制食物在能量平衡中起着重要作用 摄入量，是一个强大的食欲和脂肪生成剂在人体生理，重要的是要研究这一点 肥胖流行病中心的一个队列中的生物标志物。 Ghrelin对新陈代谢的影响被认为与瘦素相反，这两种肽激素 可能协同作用，增加胰岛素抵抗和代谢异常\瘦素测定， JHS考试1.我们建议在考试3中测定生长素释放肽和瘦素，并在考试1中测定生长素释放肽。 分析检查1生物标志物数据，结合检查3中的肥胖测量，如BMI、腰围、体重指数、体重 腰围、臀腰比以及提供内脏和皮下组织测量的成像数据。 肥胖和他们的比例，将使我们能够确定是否生物标志物发挥预测作用， 肥胖症的发展。