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.

与年龄相关的骨质疏松性骨折很大程度上是由于随着衰老和骨骼强度降低而下降的倾向增加。尽管骨骼结构有助于骨折风险，但骨矿物质密度（BMD）是骨强度和断裂风险的关键决定因素。成年人峰值骨矿物质密度的60％至80％的差异是遗传。后来的骨质疏松症是成年期间达到的峰值骨质量和损失率的峰值。在当前奖项的任期期间，我们确定了几个高度有希望的染色体区域，这些染色体区域包含影响男性和女性峰值骨骼强度的基因。该项目将重点放在三个染色体区域，其中人类和动物模型中的连锁数据都表明这些区域具有影响BMD峰值的基因。这项研究的目标是使用特征良好的位置克隆/候选方法鉴定这些基因 男人和女人的人口。这些基因的鉴定可能：1）导致预测骨质疏松症风险并允许早期预防措施的分子测试； 2）洞悉影响BMD峰值和骨质疏松症的其他因素； 3）为治疗剂提供了影响BMD的分子靶标。