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，II型糖尿病（T2D）影响了5-8％的成年人。也认识到 葡萄糖水平高于正常水平但不够高的个体过渡组 被视为糖尿病。这些人被定义为“糖尿病前”，要么受到损害 空腹葡萄糖（IFG；空腹葡萄糖100-125 mg/dl），葡萄糖耐受性受损（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强大的 与肥胖和身体不活跃的链接，其对立面也对IGT产生积极影响 和肥胖，代表着重要的护理标准疗法。 而建议的各种疾病过程的现代运动指南推荐 运动强度的最大有氧运动能力的40-85％， 最近从美国体育学院更新了体育活动和公共卫生 医学和美国心脏协会认识到，很少有研究检查 运动强度的影响。同一个小组承认，“ ...有一些迹象表明 剧烈的强度活动可能对减少心血管疾病和 早死亡比现代强度的体育锻炼...” 累积研究表明，间隔训练（INT）在 运动能力，线粒体生物发生，骨骼肌酶标记 碳水化合物代谢，有氧代谢和脂肪氧化比AER。 int涉及短 高运动强度（〜95％vo2max）的暴露（15s-2分钟），然后是恢复期 （〜50％vo2max）相等或更长的持续时间。几份报告显示INT是安全的，并且 比传统AER在临床患者中有效，包括患有周围动脉疾病的患者， 间歇性lau不平，冠状动脉疾病，充血性心力衰竭，哮喘，COPD和 较早的（> 75y）。此外，最近出版的外行新闻书《南海滩饮食》 增压：更快的体重减轻速度和改善生活已将INT带入公众 尽管缺乏临床研究证明这些书的临床研究，但众人瞩目。 使用有氧间隔调节（ISAIC）试验的胰岛素灵敏度将比较 传统的AER到INT久坐，超重/超重/肥胖的男人和糖尿病前期。这 研究将提供可能增强当前体育活动建议的信息 超重/肥胖并且患有糖尿病前的个人。 ISAIC的主要结果是 胰岛素灵敏度（ISENS）。 ISAIC的次要结果是最大的心肺适应性 （vo2max/peak）。三级结果将包括心肺适应性的亚最大指数， 人体测量法和与糖酵解，有氧代谢相关的特定机械标记， - 氧化和线粒体生物发生，包括PGC -1，GLUT4，己糖酶，柠檬酸盐 合酶，β-羟基酰基COA脱氢酶和胰岛素的丝氨酸磷酸化 受体底物1。