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.

项目概要/摘要 据估计，5-8% 的成年人患有 II 型糖尿病 (T2D)。还公认的是一个 过渡群体，其血糖水平高于正常水平，但又不足以高到 考虑糖尿病。这些人被定义为“糖尿病前期”，要么患有糖尿病 空腹血糖（IFG；空腹血糖 100-125 mg/dl）、糖耐量受损（IGT；2 小时 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 与肥胖和缺乏身体活动有关，其对立面也对 IFG/IGT 产生积极影响 和肥胖，代表了重要的标准护理治疗。 虽然针对各种疾病过程的当代运动指南建议 运动强度范围为最大有氧运动能力的 40-85%，该研究的作者 美国体育学院最近更新了体育活动和公共卫生 医学和美国心脏协会认识到，很少有研究检查过 运动强度的影响。该组织承认，“……有一些迹象表明 高强度活动可能对减少心血管疾病有更大的好处 比中等强度的身体活动更容易过早死亡……” 越来越多的研究表明，间歇训练（INT）可以产生更大的变化 运动能力、线粒体生物发生、骨骼肌酶标记物相关 碳水化合物代谢、有氧代谢和脂肪氧化均优于AER。 INT涉及短 暴露（15 秒 - 2 分钟）高强度运动（~95% VO2max），然后是恢复期 (~50% VO2max) 相同或更长的持续时间。一些报告表明 INT 是安全的 对临床患者（包括患有外周动脉疾病的患者）比传统 AER 更有效， 间歇性跛行、冠状动脉疾病、充血性心力衰竭、哮喘、慢性阻塞性肺病 老年人（>75 岁）。此外，最近出版的非专业新闻书籍《南海滩饮食》 增压：更快的减肥和更好的生活健康让 INT 走进了公众的视野 尽管缺乏临床研究证明这些书声称的好处，但它还是引起了人们的关注。 使用有氧间歇训练 (ISAIC) 试验的胰岛素敏感性将进行比较 针对久坐、超重/肥胖的糖尿病前期男性和女性，从传统 AER 到 INT。这 研究将提供的信息可能会增强当前的身体活动建议 超重/肥胖且患有糖尿病前期的人。 ISAIC 的主要成果是 胰岛素敏感性（ISens）。 ISAIC 的次要结果是最大心肺健康 （最大摄氧量/峰值）。第三个结果将包括心肺健康的次最大指数， 人体测量学，以及与糖酵解、有氧代谢相关的特定机制标记， ¿-氧化和线粒体生物合成，包括 PGC-1¿、GLUT4、己糖激酶、柠檬酸盐 合酶、β-羟酰辅酶A脱氢酶和胰岛素的丝氨酸磷酸化 受体底物-1。