Project 3

项目3

基本信息

批准号：
8102550
负责人：
BETTY P. DENNIS
金额：
$ 33.19万
依托单位：
DILLARD UNIVERSITY
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：
2010-05-16 至 2015-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8102550
关键词：
Adolescent Adult Affect African American Age Anti-Inflammatory Agents Anti-inflammatory Asthma Body Weight decreased Body fat Caloric Restriction Caucasians Caucasoid Race Child Childhood Chronic Disease Complex Control Groups DNA Data Diet Disease Exercise Exhalation Fatty acid glycerol esters Female Female Adolescents Frequencies Gastritis Genes Genetic Haplotypes Health Individual Inflammation Inflammation Mediators Inflammatory Inflammatory Response Intervention Life Link Louisiana Lung Lung Inflammation Malignant neoplasm of prostate Mediating Mediator of activation protein Metabolic Minority Morbidity - disease rate Mutation Nitric Oxide Non obese Obesity Outcome Patients Population Prevalence Production Reactive Oxygen Species Severities Severity of illness Single Nucleotide Polymorphism Solutions Symptoms Testing Therapeutic Intervention Time Waiting Lists Weight Work Youth active control airway inflammation cost cytokine diet and exercise genetic profiling high risk improved inflammatory marker inner city obesity management programs

项目摘要

The specific mechanisms linking asthma and obesity remain hypothetical. The complex matrix of pro-and-anti-inflammatory markers that explain this relationship is poorly understood. Synergistically, the severity of asthmatic symptoms and rate of morbidity intensify as obesity level increases. Therefore, obesity state may increase the production of inflammatory markers, including cytokines, which increase inflammation. In turn, the production of inflammatory markers can be regulated at the DNA level by the presence of single nucleotide polymorphisms (SNP). Our primary hypothesis is that inflammatory SNPs may regulate the degree of the inflammatory response, with obesity modifying the severity of the disease. In this instance, asthma that develops in the context of obesity demonstrates the potential deleterious relationship between a specific pro-inflammatory state (obesity) and the genetic regulators of inflammation (SNPs). Secondly, weight reduction improves the severity of asthmatic symptoms, likely through reductions in inflammation. However, the precise mechanisms that drive these positive outcomes are unknown. This consistent temporal relationship is likely related to positive alterations in lung specific inflammatory mediators and airway inflammation, which may be independently altered by diet or exercise. Or, collectively diet and exercise may reduce body fat, which in turn improves the metabolic profile, reduces reactive oxygen species and decreases inflammation. Thus, our secondary hypothesis proposes that weight loss by diet alone, but not exercise alone, will significantly reduce lung specific inflammation and diminish the pro-inflammatory responses in obese African American female adolescents with asthma compared to controls. A third exploratory hypothesis proposes that the frequency of identified SNPs will be significantly related to the fat loss through diet and/or exercise and will be mediated by specific airway and, pro- and anti-inflammatory markers. This study would allow us to define a genetic profile in African American female adolescents, which could be used to modify in advance the therapeutic interventions for asthma and obesity management and likely produce a cost-effective and time-efficient solution in these high-risk youth.

关联哮喘和肥胖的特定机制仍然假想。解释这种关系的亲抗炎性标记的复杂矩阵知之甚少。从协同上讲，随着肥胖水平的增加，哮喘症状的严重程度和发病率加剧。因此，肥胖状态可能会增加包括细胞因子在内的炎症标志物的产生，从而增加炎症。反过单核苷酸多态性（SNP）的存在。我们的主要假设是炎症性SNP可能调节炎症反应的程度，肥胖改变了疾病的严重程度。在这种情况下，在肥胖背景下发展的哮喘表明了特定的促炎状态（肥胖）与炎症遗传调节剂（SNP）之间的潜在有害关系。其次，减轻体重可以通过减少炎症来提高哮喘症状的严重程度。但是，驱动这些积极结果的确切机制尚不清楚。这种一致的时间关系可能与肺特异性炎症介质和气道炎症的积极变化有关，这可能会通过饮食或运动独立改变。或者，集体饮食和运动可以减少体内脂肪，从而改善代谢特征，减少活性氧并减少炎症。因此，我们的次要假设提出，与对照组相比，肥胖的非裔美国人雌性青少年的促炎症会大大减少肺部炎症，并减少肺部炎症的炎症并减少促炎的反应。第三个探索性假设提出，鉴定的SNP的频率将与饮食和/或运动的脂肪减少显着相关，并且将由特定的气道以及促和抗炎标记介导。这项研究将使我们能够在非洲裔美国女性青少年中定义遗传特征，这些遗传特征可用于事先修改哮喘和肥胖管理的治疗干预措施，并可能在这些高风险青年中产生具有成本效益且及时的解决方案。