BIOMEDICAL (BASIC)

髋部骨折是骨质疏松症最严重的后果，也是致残最严重的原因之一 老龄化的后果。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，以减少成年人患有骨质疏松的比例 当前的十年。这项研究的总体目标是进一步探讨 遗传识别的单核苷酸多态(SNPs)与髋部骨折及其可能的病因 髋部骨折的途径和生物标志物。我们还建议将遗传关联扩大到 主要骨骼表型与骨折风险、骨密度有关。该计划的目标 研究将：(1)确定髋部骨折的遗传变异是否类似或不同 通过分析最有希望的一组SNPs发现与骨量和瘦体重相关的SNPs 来自BMD队列的一组绝经后妇女的1-2期髋部骨折；(2) 确定一组可重复的单核苷酸多态与假想的髋部骨折的相关性 反映骨重建的新生物标志物--成骨细胞调节、钙平衡和炎症 途径；以及(3)分析髋部骨折的一组遗传和血清/血浆生物标志物，以 确定两个或多个危险因素共同预测髋部骨折风险的增加或降低 超出了每个风险因素的主要影响的预期。在结束时， 通过研究，我们将极大地促进我们对假定的功能意义的理解 与髋部骨折相关的基因变异。

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.