Genetic and behavioral effects on high-density lipoprotein: The Look AHEAD Study

高密度脂蛋白的遗传和行为影响：前瞻性研究

基本信息

批准号：
8223210
负责人：
Jeanne M McCaffery
金额：
$ 9.09万
依托单位：
MIRIAM HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8223210
关键词：
Accounting Behavior Therapy Behavioral Behavioral Genetics Blood Pressure Body Weight decreased CETP gene Cardiovascular Diseases Cardiovascular system Complement Consent Coronary artery Data Data Reporting Diabetes Mellitus Diet Education Ethnic group Exercise Funding Genes Genetic Genetic Markers Genetic Programming Genetic Risk Genotype Goals Grant Health Heart Diseases High Density Lipoprotein Cholesterol High Density Lipoproteins Hypertension Individual Individual Differences Intervention LDL Cholesterol Lipoproteins Lead Life Style Mediation Modeling Morbidity - disease rate Non-Insulin-Dependent Diabetes Mellitus Obesity Outcome Participant Persons Physical Fitness Physical activity Play Race Randomized Randomized Controlled Trials Recommendation Relative (related person)Residual state Resistance Risk Factors Role Stroke Testing Time Training Twin Studies United States National Institutes of Health Weight arm cardiovascular disorder risk cardiovascular risk factor cohort effective therapy fitness follow-up genetic analysis genome wide association study improved interest lifestyle intervention lipid metabolism mortality response success

项目摘要

DESCRIPTION (provided by applicant): At least 65% of individuals with diabetes die of some form of heart disease or stroke. This occurs despite effective treatments for certain cardiovascular risk factors, such as high low-density lipoprotein (LDL) cholesterol and hypertension. High-density lipoprotein (HDL) cholesterol is a major cardiovascular risk factor that is often low among individuals with type 2 diabetes. Behavioral interventions targeting weight and/or physical activity are well known to improve HDL. At the same time, however, genome-wide association studies (GWAS) have been successful in identifying markers associated with HDL and twin studies suggest that HDL response to behavioral intervention is heritable. In this application, we propose to determine whether well established genetic predictors of HDL also predict individual differences in HDL response to weight loss and physical activity intervention. These efforts will help identify individuals who may be resistant to HDL change in response to behavioral efforts and may lead to tailoring of interventions to optimize treatment for these individuals. Specifically, we will determine whether HDL genes (CETP, LPL, LIPC, ABCA1 and LIPG) interact with lifestyle intervention in predicting change in HDL at year 1 and 4 of the Look AHEAD trial, an NIH-funded, multi-center randomized controlled trial with the primary goal of determining whether weight loss achieved through an intensive lifestyle intervention can reduce cardiovascular morbidity and mortality among persons with type 2 diabetes (grant #DK056992). At year 1, participants assigned to Intensive Lifestyle Intervention (ILI), focusing on changes in diet and physical activity (N = 2,496; 97.1% follow-up), lost significantly more weight and showed greater improvements in fitness than individuals assigned to the Diabetes Support and Education (DSE) group (N= 2,463, 95.7% follow-up), who received diabetes support and education groups alone. The weight loss and improved fitness in the ILI at year 1 produced a significantly greater increase in HDL (7.8%), relative to DSE (2.9%). Greater increases in HDL in ILI relative to DSE are also seen at year 4. Consent for genetic analyses was provided by 3,990 participants. Genotype data for HDL markers identified from genome-wide association studies and from the IBC chip, a genotyping platform including 50,000 SNPs from ~2,600 genes relevant to cardiovascular disease, lipid metabolism, diabetes and obesity, will allow us to test our central hypothesis that genes that contribute to variability in HDL will interact with lifestyle treatment to influence changes in HDL following intensive weight loss and physical activity intervention. PUBLIC HEALTH RELEVANCE: Project Narrative Individuals with type 2 diabetes remain at increased risk for cardiovascular disease and mortality, potentially due to low high density lipoprotein (HDL) levels. Behavioral intervention, involving weight loss and physical activity, is known increase HDL. However, individuals differ in their degree of success in these programs and genetic factors may play a role. In this application, we propose to identify specific genes that predict individual differences in HDL response to behavioral intervention to help identify individuals that struggle with improving HDL despite behavioral efforts.

描述（由申请人提供）：至少有65％的糖尿病患者死于某种形式的心脏病或中风。尽管有效治疗了某些心血管危险因素，例如高密度脂蛋白（LDL）胆固醇和高血压。高密度脂蛋白（HDL）胆固醇是主要的心血管危险因素，在2型糖尿病患者中通常很低。众所周知，针对体重和/或体育活动的行为干预措施可改善HDL。然而，与此同时，全基因组关联研究（GWAS）已成功地识别与HDL相关的标记，并且双胞胎研究表明HDL对行为干预的反应是可以遗传的。在此应用中，我们建议确定HDL的良好遗传预测因子是否还可以预测HDL对体重减轻和体育活动干预的响应的个体差异。这些努力将有助于确定可能对行为努力响应HDL变化的个人，并可能导致裁缝以优化这些人的治疗方法。 Specifically, we will determine whether HDL genes (CETP, LPL, LIPC, ABCA1 and LIPG) interact with lifestyle intervention in predicting change in HDL at year 1 and 4 of the Look AHEAD trial, an NIH-funded, multi-center randomized controlled trial with the primary goal of determining whether weight loss achieved through an intensive lifestyle intervention can reduce cardiovascular morbidity and mortality among persons with type 2糖尿病（授予＃DK056992）。在第1年，分配给密集生活方式干预（ILI）的参与者着重于饮食和体育锻炼的变化（n = 2,496; 97.1％的随访），体重减轻了明显的重量，并且表现出比分配给糖尿病支持和教育组（DSE）组（n = 2,463，95.7％助产的糖尿病支持和教育的人）的健康状况的改善，他们的体重减轻了。相对于DSE（2.9％），ILI的体重减轻和提高的ILI的适应性提高了HDL（7.8％）的增加（7.8％）。在第4年，ILI相对于DSE中的HDL增加了HDL的增加。遗传分析的同意是由3,990名参与者提供。从全基因组关联研究和IBC CHIP中确定的HDL标记的基因型数据，这是一个基因分型平台，其中包括与心血管疾病，脂质代谢，糖尿病和肥胖有关的50,000个基因的50,000个SNP活动干预。公共卫生相关性：患有2型糖尿病的项目叙事人仍然存在心血管疾病和死亡率的风险增加，这可能是由于高密度脂蛋白（HDL）水平较低。涉及体重减轻和体育活动的行为干预已知增加了HDL。但是，个人在这些计划中的成功程度有所不同，遗传因素可能起作用。在此应用中，我们建议确定预测HDL对行为干预反应中个体差异的特定基因，以帮助确定尽管行为努力，但仍在改善HDL方面挣扎的个体。