Zmuda J M, Sheu Y T, Moffett S P
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
J Musculoskelet Neuronal Interact. 2006 Jan-Mar;6(1):3-15.
Osteoporosis is the most prevalent metabolic bone disease and a major clinical and public health problem. Heredity plays an important and well-established role in determining the lifetime risk of this disease. Major efforts are currently underway to identify the specific genes and their allelic variations that contribute to the heritable component to osteoporosis. A number of laboratories are using quantitative trait locus (QTL) methods of genome scanning in families and animal models to identify candidate genomic regions and, ultimately, the genes and genetic variations that lead to osteoporosis. Several chromosomal regions of the human genome have now been linked to osteoporosis-related phenotypes. Although the specific genes contributing to the majority of these linkage signals have not been identified, two positional candidate genes have now been identified: low density lipoprotein receptor-related protein 5 (LRP5) and bone morphogenetic protein 2 (BMP2). A number of QTL has also been identified by cross-breeding strains of mice with variable bone density and several of these QTL have been fine mapped, providing a rich new base for understanding osteoporosis. Genetic association analyses have also provided evidence for a modest relationship between allelic variants in several biological candidate genes and bone mass and the risk of fracture. These ongoing animal and human studies will provide a continuing source of new insight into the genetic regulation of bone and mineral metabolism and the molecular etiology of osteoporosis. The new insight that will emerge from this ongoing research should lead to new ways of diagnosing, preventing and treating the growing clinical and public health problem of osteoporosis.
骨质疏松症是最常见的代谢性骨病，也是一个主要的临床和公共卫生问题。遗传在决定这种疾病的终生风险方面起着重要且已确定的作用。目前正在做出重大努力，以确定导致骨质疏松症遗传成分的特定基因及其等位基因变异。许多实验室正在使用家族和动物模型中的基因组扫描定量性状位点（QTL）方法，来识别候选基因组区域，并最终确定导致骨质疏松症的基因和遗传变异。人类基因组的几个染色体区域现已与骨质疏松症相关表型相关联。尽管尚未确定导致这些连锁信号中大多数的具体基因，但现已确定了两个定位候选基因：低密度脂蛋白受体相关蛋白5（LRP5）和骨形态发生蛋白2（BMP2）。通过对具有可变骨密度的小鼠品系进行杂交育种，也确定了一些QTL，其中一些QTL已被精细定位，为理解骨质疏松症提供了丰富的新基础。遗传关联分析也为几个生物学候选基因中的等位基因变异与骨量及骨折风险之间的适度关系提供了证据。这些正在进行的动物和人体研究将为深入了解骨和矿物质代谢的遗传调控以及骨质疏松症的分子病因提供持续的新见解来源。这项正在进行的研究中将会出现的新见解应该会带来新的方法，用于诊断、预防和治疗日益严重的骨质疏松症临床和公共卫生问题。
