GENETIC DETERMINANTS OF PEAK BMD IN MEN & WOMEN

男性骨密度峰值的遗传决定因素

• 批准号: 7020548
• 负责人: Michael J Econs
• 金额: $ 43.54万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7020548
• 关键词: African American; aging; bone density; caucasian American; developmental genetics; family genetics; genetic polymorphism; genetic susceptibility; genetic techniques; genotype; human middle age (35-64); human subject; linkage disequilibriums; linkage mapping; osteoporosis; patient oriented research; siblings; young adult human (21-34)

Age related osteoporotic fractures are largely due to an increased propensity to fall with aging and a reduction in bone strength. Although skeletal architecture contributes to fracture risk, bone mineral density (BMD) is a critical determinant of bone strength and fracture risk. Between 60 and 80% of the variance in peak bone mineral density of adults is genetic. Osteoporosis in later life is a function of peak bone mass attained during young adulthood and rate of loss. During the tenure of the current award we have identified several highly promising chromosomal regions that contain genes that influence peak bone strength in men and women. This project will focus on three chromosomal regions where linkage data in both humans and animal models indicate that these regions harbor genes that affect peak BMD. The goals of this study are to identify these genes using a combined positional cloning/candidate approach in a well-characterized population of men and women. Identification of these genes may: 1) lead to molecular tests that predict osteoporosis risk and allow institution of early preventive measures; 2) provide insight into basic bone cell biology and other factors that affect peak BMD and predispose to osteoporosis; and 3) provide molecular targets for therapeutic agents to influence BMD.

年龄相关的骨质疏松性骨折主要是由于随着年龄的增长而增加跌倒的倾向和骨强度的降低。尽管骨骼结构会增加骨折风险，但骨矿物质密度 (BMD) 是骨强度和骨折风险的关键决定因素。成人峰值骨矿物质密度的差异有 60% 到 80% 是由遗传因素造成的。晚年骨质疏松症是青年时期达到的峰值骨量和损失率的函数。在当前奖项的任期内，我们已经确定了几个非常有前途的染色体区域，其中包含影响男性和女性峰值骨强度的基因。该项目将重点关注三个染色体区域，人类和动物模型中的连锁数据表明这些区域含有影响峰值 BMD 的基因。本研究的目标是使用组合定位克隆/候选方法以充分表征的方式鉴定这些基因。 男性和女性人口。这些基因的鉴定可能：1）进行分子测试，预测骨质疏松症风险并允许采取早期预防措施； 2) 深入了解基本骨细胞生物学以及影响峰值 BMD 和易患骨质疏松症的其他因素； 3) 为治疗药物提供影响 BMD 的分子靶点。