Do Genotype Patterns Predict Weight Loss Success for Low Carb vs. Low Fat Diets?

基因型模式是否可以预测低碳水化合物与低脂肪饮食的减肥成功？

• 批准号: 8723168
• 负责人: CHRISTOPHER D GARDNER
• 金额: $ 65.32万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-15 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8723168
• 关键词: ADRB2 gene; Address; Adult; Atkins Diet; Blood; Body Composition; Body Weight Changes; Body Weight decreased; Carbohydrates; Cells; Cheek structure; Clinic; Clinical; DEXA; DNA; Data; Data Collection; Desire for food; Diet; Dietary Carbohydrates; Dietary Fats; Energy Intake; Energy Metabolism; Enrollment; Experimental Designs; FABP2 gene; Fat-Restricted Diet; Fatty acid glycerol esters; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genomics; Genotype; Glucose; Health; Hour; Human Genome; Hunger; Individual; Insulin; Investigation; Knowledge; Link; Lipids; Macronutrients Nutrition; Medicine; Metabolic; OGTT; Obesity; Outcome; Overweight; PPARG gene; Participant; Pattern; Phenotype; Physiological; Policies; Randomized; Relative (related person); Reporting; Research; Research Design; Retrospective Studies; Satiation; Single Nucleotide Polymorphism; Swab; Testing; Variant; Woman; absorption; base; blood glucose regulation; carbohydrate metabolism; design; experience; gene environment interaction; genetic variant; genome-wide; improved; innovation; interest; lipid metabolism; men; non-diabetic; novel; ornish diet; primary outcome; programs; randomized trial; research study; response; success; therapy development; weight loss intervention

DESCRIPTION (provided by applicant): Genomics research is advancing rapidly, and links between genes and obesity continue to be discovered and better defined. A growing number of single nucleotide polymorphisms (SNPs) in multiple genes have been shown to alter an individual's response to dietary macronutrient composition. Based on prior genetic studies evaluating the body's physiological responses to dietary carbohydrates or fats, we identified multi-locus genotype patterns with SNPs from three genes (FABP2, PPARG, and ADRB2): a low carbohydrate-responsive genotype (LCG) and a low fat-responsive genotype (LFG). In a preliminary, retrospective study (using the A TO Z weight loss study data), we observed a 3-fold difference in 12-month weight loss for initially overweight women who were determined to have been appropriately matched vs. mismatched to a low carbohydrate (Low Carb) or low fat (Low Fat) diet based on their multi-locus genotype pattern. OBJECTIVE: The primary objective of this study is to confirm and expand on the preliminary results and determine if weight loss success can be increased if the dietary approach (Low Carb vs. Low Fat) is appropriately matched to an individual's genetic predisposition (LCG vs. LFG) toward those diets. This study will target both women and men (the A TO Z study involved only women), and address a set of specific aims intended to further elaborate on potential mechanisms and the clinical utility of these results. A new secondary aim has been added to this resubmitted application that will involve a rigorous exploratory investigation of additional SNPs that have shown genome-wide significant associations with obesity and metabolic phenotypes that might improve on the 3-SNP signature. DESIGN: The main study is a randomized trial employing a 2X2 parallel design to test the central hypothesis that there will be greater weight loss when 320 overweight/obese non- diabetic adults are matched vs. mismatched by genetic predisposition (LCG vs. LFG) to a 12-month Low Carb vs. Low Fat weight loss diet (n=80/cell). Participants will be genotyped prior to randomization, and blinding will be maintained for the genotyping results for both participants and data collectors during the study. Other than the primary outcome of weight change, which will be assessed monthly, primary data collection will occur at 0, 3, 6, and 12 months and include energy intake (3-day unannounced 24-hour recalls, NDS-R), appetite/satiety/hunger, energy expenditure (resting energy expenditure), body composition (DEXA), and blood variables (lipids, insulin, glucose, OGTT). IMPACT: If the intriguing preliminary retrospective results are confirmed in this full scale study, the results will demonstrate that inexpensive DNA testing could help dieters predict whether they will have greater weight loss success on a Low Carb or a Low Fat diet. Commensurate with increasing scientific interest in personalized medicine approaches to intervention development, this would provide an example of the potentially substantial health impacts that could be obtained through understanding specific gene-environment interactions that have been anticipated from the unraveling of the human genome.

描述（由申请人提供）：基因组学研究正在迅速发展，基因与肥胖之间的联系继续被发现并更好地定义。越来越多的多种基因中的单核苷酸多态性（SNP）已被证明会改变个人对饮食大量营养素组成的反应。基于先前评估人体对饮食碳水化合物或脂肪的生理反应的遗传研究，我们使用来自三个基因（FabP2，PPARG和ADRB2）的SNP鉴定了多层次的基因型模式：低碳水化合物 - 碳水化合物 - 反应性基因型（LCG）（LCG）和低脂肪逆转基因型（低脂肪 - 逆转基因型）。在一项初步的回顾性研究（使用A到Z减肥研究数据）中，我们观察到最初的超重女性的12个月体重减轻差异为3倍，这些女性确定与低碳水化合物（低碳水化合物）或低脂肪（低脂肪）或基于其多型基因型基因类型模式相匹配的与不匹配的低碳水化合物（低脂肪（低脂肪））。目的：这项研究的主要目标是确认和扩展初步结果，并确定如果将饮食方法（低碳水化合物与低脂）适当地与个人的遗传倾向（LCG与LFG）适应这些饮食，是否可以增加体重成功。这项研究将针对男性和男性（A到Z研究仅涉及女性），并针对一系列特定目标，旨在进一步详细介绍这些结果的潜在机制和临床实用性。该重新提交的应用已添加了一个新的次要目的，该目标将涉及对其他SNP进行严格的探索性研究，这些SNP已显示出与肥胖和代谢表型的重要相关性，这些相关性可能会改善3-SNP签名。设计：主要研究是一项随机试验，该试验采用2x2平行设计，以测试中心假设，即当320个超重/肥胖的非糖尿病成年人与遗传性倾向（LCG与LFG）相匹配时，体重减轻将会更大，与12个月的低碳水化合物减肥饮食（LCG vs. LFG）相匹配。参与者将在随机分类前进行基因分型，并在研究期间为参与者和数据收集者的基因分型结果保持盲目性。 Other than the primary outcome of weight change, which will be assessed monthly, primary data collection will occur at 0, 3, 6, and 12 months and include energy intake (3-day unannounced 24-hour recalls, NDS-R), appetite/satiety/hunger, energy expenditure (resting energy expenditure), body composition (DEXA), and blood variables (lipids, insulin, glucose, OGTT).影响：如果在这项全面研究中证实了有趣的初步回顾性结果，则结果将表明，廉价的DNA测试可以帮助减肥者预测他们在低碳水化合物还是低脂肪饮食上是否会获得更大的体重减轻成功。与对个性化医学方法开发的个性化医学方法的越来越多的科学兴趣相称，这将提供一个例子，说明可以通过理解特定的基因环境相互作用来获得潜在的实质性健康影响，这些相互作用已预期的是人类基因组的揭露。