Genetic Epidemiology of Bone Turnover Markers

在美国，超过2500万人患有骨质疏松症。骨质疏松症是一种复杂的衰老疾病，可能归因于几种尚未确定的遗传和环境影响。与青春期后开始生长的身体其他组织不同，骨组织在一个被称为重塑的过程中不断生长和吸收。在成人的大部分生命中，生长和吸收速率处于平衡状态。然而，在老年时，骨吸收的速度超过了新骨形成的速度。其结果是骨矿物质密度的逐渐丧失，导致骨脆弱性增加。本研究的总体目标是收集参与Fels纵向研究的500名成年家庭成员的骨转换标志物的初步数据，以便通过定量遗传分析确定遗传对这些性状的影响性质。这项为期一年的试点资助的结果将作为一个更大的R01应用分析的基础。这项为期一年的试点资助的结果将作为更大的R01申请的基础，其主要研究目标是分离和定位影响骨矿物质密度正常变异和相关表型的特定基因。对于拟议的试点研究，将使用市售试剂盒从储存的血清样本中检测几种骨转换标记物。这些检测包括骨特异性碱性磷酸酶、骨钙素、吡啶啉交联、总脱氧吡啶啉交联、I型胶原c端前肽和YKL-40。所有这些骨质流失的测量，然而很少有研究集中在理解这些性状表型变异的遗传基础上。本研究的工作假设是遗传因素影响骨转换的正常定量变化。此外，基因对骨转换测量的影响最终影响骨矿物质密度和随后的骨质疏松症风险。

More than 25 million people suffer from osteoporosis in the United States. Osteoporosis is a complex disease of aging that is likely to be attributable to several as yet unidentified genetic and environmental influences. Unlike other tissues in the body that cause to grow after adolescence, bone tissue is continuously growing and resorbing in a process known as remodeling. During most of adult life, growth and resorption rates are in equilibrium. At older ages, however, the rate of resorption outpaces the rate of new bone formation. The result is a progressive loss of bone mineral density leading to increased bone fragility. The overall objective of this study is to collect preliminary data on bone turnover markers in 500 adult family members participating in the Fels Longitudinal Study in order to determine the nature of genetic effects on these traits using quantitative genetic analysis. The results of this one-year pilot grant will be used as the foundation for a larger R01 application analysis. The results of this one-year pilot grant will be used as the foundation for a larger R01 application with a primary research goal of isolating and locating specific genes influencing normal variation in bone mineral density and related phenotypes. For the proposed pilot study, several markers of bone turnover will be assayed from stored serum samples using commercially available kits. These assays include bone-specific alkaline phosphatase, osteocalcin, pyridinoline crosslinks, total deoxypyridinoline crosslinks, C-terminal propeptide of type I collagen and YKL-40. All of these measures of bone loss, yet little research has focused on understanding the genetic basic of phenotypic variation in these traits. The working hypothesis of the proposed study is that genetic factors influence normal quantitative variation in bone turnover. And further, genetic effects on measures of bone turnover ultimately influences bone mineral density and subsequent risk for osteoporosis.