Vitamin D related genes and developmental origins of cardiometabolic risk

维生素 D 相关基因和心脏代谢风险的发育起源

• 批准号: 8470221
• 负责人: Daniel Asmamaw Enquobahrie
• 金额: $ 13.25万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8470221
• 关键词: Academia; Accounting; Address; Adult; Area; Biological Markers; Biomedical Research; Birth Weight; Candidate Disease Gene; Cardiovascular Diseases; Cardiovascular system; Clinical; DNA; Data; Development; Developmental Gene; Disease; Early Diagnosis; Early treatment; Environment; Epidemiologist; Faculty; Fatty Acids; Funding; Gene Expression; Gene-Modified; Genes; Genetic Predisposition to Disease; Genetic Risk; Genetic Variation; Genotype; Hypertension; Insulin Resistance; Interdisciplinary Study; K-Series Research Career Programs; Lipids; Lipoproteins; Measurement; Mentors; Metabolism; Mothers; Obesity; Pathway interactions; Perinatal; Perinatal Epidemiology; Population Study; Preparation; Prevention; Research; Risk; Risk Factors; Role; Serum; Specimen; Sum; Tissue-Specific Gene Expression; Training; Umbilical Cord Blood; Underrepresented Minority; United States National Institutes of Health; Variant; Vitamin D; Whole Blood; abstracting; career; experience; genetic epidemiology; genetic risk factor; glucose metabolism; novel; nutrition; nutritional epidemiology; obesity risk; offspring; peripheral blood; public health relevance; reproductive epidemiology; response; skills; young adult

DESCRIPTION (provided by applicant): This K01 application is in response to the "Mentored Career Development Award to Promote Faculty Diversity/Re-entry in Biomedical Research" (RFA-HL-10-012). The applicant seeks to develop an inter-disciplinary research career focused on the role of genetic susceptibility and environment in the developmental origins of adult cardiometabolic risk, building directly upon his previous training/experience in cardiovascular, reproductive, perinatal, nutritional and genetic epidemiology. Mounting evidence supports the developmental origins of cardiometabolic risk. Additionally, low vitamin D levels are associated with cardiometabolic risk factors. However, whether variations in vitamin D metabolism related genes and/or variations in genes differentially expressed in offspring with low vitamin D levels, account, in part, for the developmental origins of adult cardiometabolic risk is largely unknown. The applicant will use biologic specimens, clinical and examination data from mother and offspring diads from two well characterized study populations (the NIH funded Jerusalem Perinatal Study and the Omega Study) to examine vitamin D metabolism related genetic variations and cardiometabolic risk. Using tag-SNPs, the applicant will evaluate associations of common variations in a priori identified 5 candidate genes in vitamin D metabolism (LRP2, CUBN, CYP27B1, GC and VDR) with birth weight, and cardiometabolic risk factors, including obesity, insulin resistance, lipids and lipoproteins, and high blood pressure in young adults. In a pilot global whole blood gene expression study, using 1) cord blood and 2) peripheral blood from offspring with high/low vitamin D levels, the applicant will identify a set of novel candidate genes in fatty acid and glucose metabolism pathways related to vitamin D metabolism. The applicant then will examine associations of variations in these novel candidate genes in mothers and offspring with offspring birth weight and cardiometabolic risk in young adults. Secondarily, the applicant will evaluate whether variations in candidate/novel genes modify the associations of 25-hydroxy vitamin D to examine a set of hypothesis involving vitamin D metabolism related genetic risk factors and developmental origins of cardiometabolic risk. The candidate also has developed a mentoring framework with expertise in areas relevant to his research agenda that will help the candidate develop the capabilities needed to make unique contributions by conducting high quality and high impact interdisciplinary research related to gene-environment (nutrition) interactions and developmental origins of cardiometabolic diseases, levels with cardiometabolic risk. In sum, the findings from these studies will allow the candidate to examine a set of hypothesis involving vitamin D metabolism related genetic risk factors and developmental origins of cardiometabolic risk. The candidate also has developed a mentoring framework with expertise in areas relevant to his research agenda that will help the candidate develop the capabilities needed to make unique contributions by conducting high quality and high impact interdisciplinary research related to gene-environment (nutrition) interactions and developmental origins of cardiometabolic diseases.

描述（由申请人提供）：此K01申请响应“促进生物医学研究的教师多样性/重新进入的“指导职业发展奖”（RFA-HL-10-0-012）。申请人试图发展跨学科研究职业，重点是遗传易感性和环境在成人心脏代谢风险的发展起源中的作用，直接基于他先前在心血管，生殖，围产期，营养，营养和遗传流行病学方面的培训/经验。安装证据支持心脏代谢风险的发育起源。另外，低维生素D水平与心脏代谢危险因素有关。但是，维生素D代谢相关的基因的变异和/或在较低维生素D水平的后代差异表达的基因的变异是否，部分原因是成人心脏代谢风险的发育起源在很大程度上是未知的。申请人将使用来自两个良好特征的研究人群（NIH资助的耶路撒冷欧洲围产期研究和欧米茄研究）的母亲和后代的生物标本，临床和检查数据来检查与维生素D代谢相关的遗传变异和心脏代谢风险。使用TAG-SNP，申请人将评估先验中的常见变化的关联，确定了维生素D代谢中的5种候选基因（LRP2，CUBN，CYP27B1，GC和VDR）与出生体重，以及心脏代谢的危险，包括肥胖，胰岛素抵抗，胰岛素抵抗，脂肪蛋白和脂肪蛋白和高戒烟，以及年轻人的肥胖症，包括肥胖，抗肥胖风险因素。在一项试验全球全血基因表达研究中，使用1）脐带血和2）来自高/低维生素D水平的后代的外周血，申请人将确定脂肪酸和葡萄糖代谢途径与维生素D代谢相关的一组新型候选基因。然后，申请人将检查母亲和后代的这些新型候选基因的变化关联，其后代出生体重和年轻人的心脏代谢风险。其次，申请人将评估候选/新型基因的变化是否修改了25-羟基维生素D的关联，以检查一组涉及维生素D代谢相关的遗传风险因素和心脏代谢风险的发育起源的假设。候选人还开发了一个指导框架，具有与他的研究议程相关领域的专业知识，这将有助于候选人通过进行高质量和高影响力的跨跨学科研究所需的能力来做出独特的贡献（营养）相互作用（营养）相互作用以及与心脏代谢量的心脏代谢性疾病的发展起源，并具有与心脏代谢级别的水平。 总而言之，这些研究的发现将使候选人可以检查一组涉及维生素D代谢相关的遗传危险因素和心脏代谢风险的发育起源的假设。候选人还开发了一个指导框架，具有与他的研究议程相关领域的专业知识，这将有助于候选人通过进行与基因环境（Nutriention）相互作用（营养）相互作用和心脏局部情况疾病的发展起源相关的高质量和高影响力跨学科研究所需的能力。