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不断被发现并得到更好的定义。多个基因中越来越多的单核苷酸多态性 (SNP) 已被证明可以改变个体对膳食大量营养素成分的反应。根据之前评估人体对膳食碳水化合物或脂肪的生理反应的遗传学研究，我们通过来自三个基因（FABP2、PPARG 和 ADRB2）的 SNP 确定了多位点基因型模式：低碳水化合物反应基因型 (LCG) 和低脂肪基因型-响应基因型（LFG）。在一项初步回顾性研究（使用 A TO Z 减肥研究数据）中，我们观察到最初超重的女性在 12 个月内的体重减轻有 3 倍的差异，这些女性被确定为与低碳水化合物适当匹配与不匹配（低碳水化合物）或低脂肪（低脂肪）饮食基于其多位点基因型模式。目的：本研究的主要目的是确认和扩展初步结果，并确定如果饮食方法（低碳水化合物与低脂肪）与个人的遗传倾向（LCG 与低脂饮食）适当匹配，是否可以提高减肥成功率。 LFG）针对这些饮食。这项研究将针对女性和男性（A TO Z 研究仅涉及女性），并解决一系列具体目标，旨在进一步阐述这些结果的潜在机制和临床效用。重新提交的申请中添加了一个新的次要目标，其中将涉及对其他 SNP 进行严格的探索性调查，这些 SNP 已显示出与肥胖和代谢表型在全基因组范围内的显着关联，可能会改善 3-SNP 特征。设计：主要研究是一项随机试验，采用 2X2 平行设计来测试中心假设，即当 320 名超重/肥胖非糖尿病成年人与遗传易感性（LCG 与 LFG）匹配或不匹配时，体重减轻会更大。 12 个月的低碳水化合物与低脂肪减肥饮食（n=80/细胞）。在随机化之前将对参与者进行基因分型，并且在研究期间对参与者和数据收集者的基因分型结果将保持盲法。除了每月评估一次的体重变化的主要结果外，主要数据收集将在第 0、3、6 和 12 个月时进行，包括能量摄入量（3 天未通知的 24 小时召回，NDS-R）、食欲/饱腹感/饥饿、能量消耗（静息能量消耗）、身体成分（DEXA）和血液变量（血脂、胰岛素、葡萄糖、OGTT）。影响：如果有趣的初步回顾性结果在这项全面研究中得到证实，结果将证明廉价的 DNA 测试可以帮助节食者预测他们是否会通过低碳水化合物或低脂肪饮食获得更大的减肥成功。与对干预开发的个性化医学方法日益增长的科学兴趣相称，这将提供一个潜在的重大健康影响的例子，通过了解人类基因组的揭示所预期的特定基因与环境的相互作用，可以获得潜在的重大健康影响。