Genetic Epidemiology of Bone Turnover Markers

美国有超过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，很可能归因于几个尚不确定的遗传和环境影响。与青春期后导致生长的身体其他组织不同，骨组织在一个称为重塑的过程中不断生长和重新吸收。在成年的大部分时间里，生长和吸收的速度是平衡的。然而，在较年长的人中，吸收的速度超过了新骨形成的速度。其结果是骨密度的进行性丧失，导致骨脆性增加。这项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记的初步数据，以便使用定量遗传分析来确定这些性状的遗传效应的性质。这一为期一年的试点赠款的结果将被用作更大规模的R01应用分析的基础。这一为期一年的试点拨款的结果将被用作更大规模的R01应用的基础，主要研究目标是分离和定位影响骨密度正常变化和相关表型的特定基因。在拟议的试点研究中，将使用商用试剂盒从储存的血清样本中分析几个骨转换的标志物。这些检测包括骨特异性碱性磷酸酶、骨钙素、吡啶类交联物、总脱氧吡啶类交联物、I型胶原C末端前肽和YKL-40。所有这些衡量骨质流失的指标，但很少有研究集中于了解这些特征表型变异的遗传基础。这项研究的工作假设是，遗传因素影响骨转换的正常数量变化。此外，骨转换指标的遗传效应最终会影响骨密度和随后发生骨质疏松症的风险。

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.