Ghrelin, PAil and Their Associations with Adipokine

本意见书回应了RFA关于试探性的NCMHD卓越中心(RFA-MD-08- 0049)。我们建议检查两个生物标志物的分布，在一个大的，正在进行的，特征良好的 对非裔美国人的纵向研究，杰克逊心脏研究，并表征他们与 代谢综合征(METS)、2型糖尿病(T2D)和 心血管疾病(CVD)，长期目标是更准确地识别 将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评估家族史的相关性。除了检查 血浆Ghrelin和PAI-1的水平，我们希望在其他危险因素的背景下对它们进行检查，包括 GWAS分析中的肥胖和遗传风险因素。 具体地说，本研究旨在描述血浆Ghrelin和PAI-1水平的分布及其相互关系。 杰克逊心脏研究(JHS)队列中的遗传性，检查环境和遗传相关性 在JHS队列中血浆Ghrelin和PAI-1水平与心脏病预测因素之间的关系，并发现 JHS中与血浆Ghrelin和PAI-1水平相关的多态和单倍型。 因为Ghrelin通过控制食物，通过下丘脑在能量平衡中发挥重要作用 摄入，在人体生理中是一种强大的促食欲素和成脂剂，对此进行研究具有重要意义 肥胖症流行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，而这两种肽激素 可能协同作用增加胰岛素抵抗和代谢异常 JHS试验1。我们建议在试验3中同时测定Ghrelin和Leptin，并在试验1中测定Ghrelin。 分析检查1中的生物标记物数据与检查3中的肥胖测量，如BMI、腰围 周长、臀围与腰围之比，以及提供内脏和皮下测量的影像数据 肥胖症及其比率，将使我们能够确定生物标志物是否在 肥胖的发展。

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.