Genome-wide Association Study: Fetal Hemoglobin Phenotypes in Sickle Cell Disease

全基因组关联研究：镰状细胞病中的胎儿血红蛋白表型

• 批准号: 7785754
• 负责人: Betty Sue Pace
• 金额: $ 7.65万
• 依托单位: UNIVERSITY OF TEXAS DALLAS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7785754
• 关键词: 3-Hydroxyacyl-CoA dehydrogenase; Adult; Aerobic; Aerobic Exercise; Affect; African American; Algorithms; American; American Heart Association; Anthropometry; Asthma; Binding; Biogenesis; Birth; Body Weight decreased; Books; CREB1 gene; Cardiovascular Diseases; Caring; Cell Respiration; Chi-Square Tests; Chromosomes, Human, Pair 11; Chronic Obstructive Airway Disease; Citrate (si)-Synthase; Clinical; Clinical Research; Congestive Heart Failure; Coronary Arteriosclerosis; Custom; DNA; DNA-Protein Interaction; Data; Databases; Development; Diabetes Mellitus; Disease; Distant; Elderly; Elements; Enrollment; Erythroid; Exercise; Experimental Designs; Fatty acid glycerol esters; Fetal Hemoglobin; GLUT4 gene; Gene Expression; Gene Expression Regulation; Gene Targeting; Genes; Genetic; Genetic Markers; Genetic Transcription; Genetic Variation; Genomics; Globin; Glucose; Glycolysis; Guidelines; Haplotypes; Health; Hemoglobin; Hemoglobin concentration result; Hemoglobinopathies; Impaired fasting glycaemia; Individual; Inherited; Intermittent Claudication; Life; Link; Linkage Disequilibrium; Maps; Mitochondria; Molecular; Mutation; NIH Program Announcements; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Overweight; Patients; Peripheral arterial disease; Persons; Phase; Phenotype; Phosphorylation; Physical activity; Polymorphism Analysis; Prediabetes syndrome; Premature Mortality; Process; Proteins; Public Health; Publications; Publishing; Quantitative Trait Loci; Recommendation; Recovery; Regulation; Reporting; Research; Risk; Role; Sampling; Serine; Sickle Cell Anemia; Single Nucleotide Polymorphism; Single Nucleotide Polymorphism Map; Skeletal Muscle; South Beach Diet; Sports Medicine; Structure; Structure-Activity Relationship; Symptoms; Techniques; Testing; Thalassemia; Training; Update; Woman; abstracting; base; carbohydrate metabolism; case control; chromatin immunoprecipitation; clinical phenotype; cohort; college; conditioning; cooperative study; density; design; expectation; fasting glucose; fitness; functional genomics; gene therapy; genome wide association study; genome-wide; hexokinase; impaired glucose tolerance; improved; in vivo; indexing; innovation; insight; insulin receptor substrate 1 protein; insulin sensitivity; men; oxidation; primary outcome; promoter; response; secondary outcome; sedentary; therapy development

Project Summary/Abstract It is estimated that type II diabetes (T2D) affects 5-8% of adults. Also recognized is a transitional group of individuals whose glucose levels are above normal, yet not high enough to be considered diabetes. Defined as "pre-diabetes," these individuals are either have impaired fasting glucose (IFG; fasting glucose 100-125 mg/dl), impaired glucose tolerance (IGT; 2-h glucose 140-199 mg/dl) or both. Two unifying features associated with pre-diabetes is a strong link to obesity and physical inactivity, the antithesis of which also positively influences IFG/IGT and obesity, representing an important standard-of-care therapy. While contemporary exercise guidelines for various diseases processes recommend exercise intensity ranges from 40-85% of maximal aerobic exercise capacity, the authors of the recently updated Physical Activity and Public Health from the American College of Sports Medicine and the American Heart Association recognize that few studies have examined the effects of exercise intensity. This same group acknowledges that, "...there is some indication that vigorous-intensity activities may have greater benefit for reducing cardiovascular disease and premature mortality than moderate-intensity physical activity..." Accumulating research shows that interval training (INT) produces greater changes in exercise capacity, mitochondrial biogenesis, skeletal muscle enzymatic markers associated with carbohydrate metabolism, aerobic metabolism and fat oxidation than AER. INT involves short exposures (15s - 2 min) of high exercise intensity (~95% VO2max) followed by a recovery period (~50% VO2max) of equal or longer duration. Several reports have shown INT to be safe and effective than traditional AER in clinical patients including those with peripheral artery disease, intermittent claudication, coronary artery disease, congestive heart failure, asthma, COPD, and the elderly (>75y). Further, the recent publication of the lay press book, The South Beach Diet Supercharged: Faster Weight Loss and Better Health for Life has brought INT into the public limelight despite the paucity of clinical studies attesting to the books purported benefits. The Insulin Sensitivity using Aerobic Interval Conditioning (ISAIC) trial will compare traditional AER to INT in sedentary, overweight/obese men and women with pre-diabetes. This study will provide information that may enhance current physical activity recommendations for individuals who are overweight/obese and have pre-diabetes. The primary outcome for ISAIC is insulin sensitivity (ISens). The secondary outcome for ISAIC is maximal cardiorespiratory fitness (VO2max/peak). Tertiary outcomes will include sub-maximal indices of cardiorespiratory fitness, anthropometry, and specific mechanistic markers associated with glycolysis, aerobic metabolism, ¿-oxidation, and mitochondrial biogenesis inclusive of PGC-1¿, GLUT4, hexokinase, citrate synthase, beta-hydroxyacyl CoA dehydrogenase, and the serine phosphorylation of insulin receptor substrate-1.

项目摘要/摘要 据估计，2型糖尿病(T2D)影响5-8%的成年人。同样被认可的还有一种 血糖水平高于正常，但还不足以 被认为是糖尿病。这些人被定义为“糖尿病前期”，要么是已经受损 空腹血糖(IFG；空腹血糖100-125 mg/dl)，糖耐量减低(IGT；2-h 葡萄糖140-199 mg/dl)或两者兼而有之。与糖尿病前期相关的两个统一特征是一个强有力的 与肥胖和缺乏运动有关，它们的对立面也对IFG/IGT有积极影响 和肥胖症，代表着一种重要的护理标准疗法。 虽然当代针对各种疾病的锻炼指南建议 运动强度从最大有氧运动量的40%到85%不等，作者们 美国体育学院最近更新的体育活动和公共健康 医学和美国心脏协会认识到，很少有研究研究 运动强度的影响。这个团体也承认，“……有一些迹象表明 剧烈运动可能对减少心血管疾病和 过早死亡，而不是中等强度的体力活动。 越来越多的研究表明，间歇训练(INT)对 运动能力、线粒体生物发生、骨骼肌酶标记物 碳水化合物代谢、有氧代谢和脂肪氧化均优于AER。INT涉及空头 高强度运动(~95%最大摄氧量)的暴露(15s-2分钟)，然后是恢复期 (~50%最大摄氧量)持续时间相同或更长。几份报告显示INT是安全的 在包括外周动脉疾病在内的临床患者中比传统的AER有效， 间歇性跛行、冠状动脉疾病、充血性心力衰竭、哮喘、COPD和 老年人(&gt；75y)。此外，最近出版了一本名为《南滩饮食》的非专业新闻书籍 超负荷：更快的减肥和更健康的生活将INT带入公众 尽管很少有临床研究证明这些书声称有好处，但它仍然备受瞩目。 使用有氧间歇调节(ISAIC)的胰岛素敏感性试验将进行比较 传统的AER适用于久坐不动、超重/肥胖的糖尿病前期男性和女性。这 这项研究将提供信息，可能会加强目前的身体锻炼建议 超重/肥胖并有糖尿病前期症状的个人。ISAIC的主要结果是 胰岛素敏感性(ISens)。ISAIC的次要结果是最大限度的心肺健康 (最大摄氧量/峰值)。三级结果将包括心肺健康指数低于最大值， 人体测量，以及与糖酵解、有氧代谢、 氧化和线粒体生物发生，包括PGC-1、GLUT4、己糖激酶、柠檬酸 合成酶、β-羟基酰辅酶A脱氢酶与胰岛素的丝氨酸磷酸化 受体底物-1。