Genetics, Environment and Weight Gain Posttransplant

遗传学、环境和移植后体重增加

• 批准号: 7849106
• 负责人: Ann King Cashion
• 金额: $ 3.55万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-14 至 2010-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7849106
• 关键词: Adipose tissue; Adult; African American; American; Bayesian Analysis; Bioinformatics; Body mass index; Candidate Disease Gene; Cardiovascular Diseases; Caring; Cessation of life; Chronic Disease; Classification; Clinical; Data; Dependency; Development; Diabetes Mellitus; Eating; Environment; Environmental Risk Factor; Epidemic; Female; Gene Expression; Gene Expression Profiling; General Population; Genes; Genetic; Genomics; Goals; Health Status; Healthcare; Healthy People 2010; Hypertension; Immunosuppressive Agents; Individual; Kidney Transplantation; Literature; Medical; Methodology; Microarray Analysis; Modeling; Molecular; Molecular Profiling; Morbidity - disease rate; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Pathway interactions; Pharmaceutical Preparations; Physical activity; Play; Polymerase Chain Reaction; Population; Prevention; Preventive; Regulatory Element; Research; Research Personnel; Risk; Risk Factors; Role; Susceptibility Gene; Technology; Time; Transcript; Transplant Recipients; Transplantation; Weight Gain; base; computer based statistical methods; cost; demographics; design; experience; gene environment interaction; improved; innovation; insight; interdisciplinary approach; mortality; network models; novel; obesity risk; obesity treatment; programs; prospective; psychosocial

DESCRIPTION (provided by applicant): Obesity, a growing epidemic in the US and a health care priority in Healthy People 2010, is a risk factor for type 2 diabetes mellitus, cardiovascular disease and other chronic diseases in renal transplant recipients. Renal transplant recipients gain an average of 22 Ibs during the first year following transplant, which is significantly more than the 2 Ibs average weight gain in US adults. In addition, African American (AA) females are most at risk for weight gain and morbidity. This predictable and significant weight gain within a short amount of time, particularly in AAs, and its association with morbidity and mortality makes this a high priority concern. The purpose of this application is to prospectively examine genetic (gene expression) and environmental factors (food intake, physical activity, demographic, health status, psychosocial) contributing to obesity at one year following renal transplantation in recipients who are non-obese at time of transplant. Long-term goals include prevention and treatment of obesity in recipients. Our hypothesis is that gene- environmental interactions can predict whether individuals will become obese at one year post transplant. Specifically we will (1) identify up to 10 environmental factors associated with post transplant obesity, (2) identify up to 10 gene expressions associated with obesity, (3) use Bayesian analysis to determine combinations of gene- environment interactions that predict obesity. A prospective design will be used to compare genetic and environmental factors and clinical outcomes at baseline, 3, 6, 12 and 24 months post transplant. Gene expression profiling using microarray analysis and real-time polymerase chain reaction on adipose tissue will be used to identify key regulatory elements that play a major role in obesity. Bayesian Network modeling will be used to investigate causal relationships. This significant and innovative study incorporates an interdisciplinary approach to combine emerging genomic and bioinformatic technologies with traditional methodologies to explicate key gene-environment interactions responsible for post transplant obesity. The relevance of this study is that findings will assist health care practitioners in caring for renal transplant recipients so that they do not gain weight and become obese following renal transplantation. This will result in fewer health care problems following transplantation.

描述（由申请人提供）：肥胖症，美国越来越多的流行病以及健康人的卫生保健优先事项，是2型糖尿病，心血管疾病和肾移植接受者中其他慢性疾病的危险因素。移植后的第一年，肾移植接受者平均获得22 ibs，这明显高于美国成年人的2 ibs平均体重增加。此外，非洲裔美国人（AA）女性最有可能增加体重和发病率的风险。这种可预测且显着的体重增加在短时间内，尤其是在AAS中及其与发病率和死亡率的关联，这使得这是一个很高的优先考虑。本应用的目的是前瞻性检查遗传（基因表达）和环境因素（食物摄入，体育锻炼，人口统计学，健康状况，社会心理），在肾移植后一年有助于肥胖，而在移植时非肥胖者则是肥胖。长期目标包括预防和治疗接受者的肥胖症。我们的假设是，基因环境相互作用可以预测移植后一年是否会肥胖。具体而言，我们将（1）确定多达10个与移植后肥胖相关的环境因素，（2）确定多达10个与肥胖相关的基因表达，（3）使用贝叶斯分析来确定预测肥胖症的基因环境相互作用的组合。前瞻性设计将用于比较移植后3、6、12和24个月基线时的遗传和环境因素和临床结果。使用微阵列分析和脂肪组织上的实时聚合酶链反应进行基因表达分析将用于识别在肥胖症中起主要作用的关键调节元件。贝叶斯网络建模将用于研究因果关系。这项重要而创新的研究结合了一种跨学科方法，将新兴的基因组和生物信息学技术与传统方法结合起来，以解释负责移植后肥胖的关键基因环境相互作用。这项研究的相关性是，发现将有助于医疗保健从业人员照顾肾移植接受者，以免在肾移植后体重增加并肥胖。这将导致移植后减少医疗保健问题。