BIOMEDICAL (BASIC)

生物医学（基础）

• 批准号: 7938482
• 负责人: REBECCA JACKSON
• 金额: $ 160.48万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-01-15 至 2011-01-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7938482
• 关键词: BIOMEDICAL; BASIC

Hip fractures are the most serious outcome of osteoporosis and one of the most disabling consequences of aging. In order to reduce the burden of this disease, the Healthy People 2010 objectives establish a national target to reduce the proportion of adults who have osteoporosis during the current decade. The overarching goal of this study is to further explore the relationship between genetically identified single nucleotide polymorphisms (SNPs) for hip fracture and putative causal pathways and biomarkers for hip fracture. We also propose to extend the genetic associations to a major skeletal phenotype associated with fracture risk, bone mineral density. The objectives of the study wil be to: (1) determine whether the genetic variants for hip fracture are similar to or differ from SNPs associated with bone mass and lean body mass by analyzing the most promising panel of SNPs from the Phase 1-2 hip fracture GWAS in a subset of postmenopausal women from the BMD cohort; (2) identify the association of a reproducible set of SNP's from the GWAS for hip fracture with putative novel biomarkers reflecting bone remodeling-osteoblast regulation, calcium balance, and inflammatory pathways; and (3) to analyze the set of genetic and serum/plasma biomarkers for hip fracture to determine whether two or more risk factors together predict hip fracture increased or decreased risk beyond what would be expected from the main effects of each risk factor. At the conclusion of the study, we wil have significantly advanced our understanding of the putative functional significance of genetic variants associated with hip fracture.

髋部骨折是骨质疏松症最严重的后果，也是最致残的疾病之一。 老化的后果。为了减轻这种疾病的负担，2010年健康人 目标建立一个国家目标，以减少成年人谁拥有骨质疏松症的比例， 当前的十年。本研究的总体目标是进一步探讨 髋部骨折的单核苷酸多态性（SNPs）和假定的因果关系 髋部骨折的途径和生物标志物。我们还建议将遗传关联扩展到 与骨折风险、骨密度相关的主要骨骼表型。的目标 研究将：（1）确定髋部骨折的遗传变异是否与 通过分析最有希望的SNPs组，发现与骨量和瘦体重相关的SNPs 来自BMD队列绝经后女性亚组的1-2期髋部骨折GWAS;（2） 鉴定来自GWAS的一组可重复的SNP与髋部骨折的推定的 反映骨重建-成骨细胞调节、钙平衡和炎症的新生物标志物 途径;和（3）分析髋部骨折的遗传和血清/血浆生物标志物的集合， 确定两个或两个以上的风险因素是否共同预测髋部骨折风险增加或减少 超出了每个风险因素的主要影响的预期。结束时 通过这项研究，我们将大大提高我们对假定的功能意义的理解， 与髋骨骨折相关的遗传变异