Ralston S H
Department of Medicine and Therapeutics, University of Aberdeen, UK.
QJM. 1997 Apr;90(4):247-51. doi: 10.1093/qjmed/90.4.247.
Genetic factors play an important role in the pathogenesis of osteoporosis--a common condition characterized by reduced bone mass and increased fracture risk. Twin and family studies suggest that up to 85% of the variance in bone mineral density is genetically determined, and molecular genetic studies have identified several candidate genes which may be involved in this process. The vitamin D receptor gene (VDR) has been most widely studied, but the relationship between VDR polymorphisms and bone density is inconsistent, and poorly reproducible in different populations. Polymorphisms in and around other candidate genes have also been associated with bone mass, but the most promising candidate so far identified is the collagen type 1 alpha gene. A polymorphism in the regulatory region of this gene has recently been described which affects a recognition site for the transcription factor Sp1. This polymorphism is associated, not only with bone mass, but also with bone loss and the clinically important condition of osteoporotic fracture. Since osteoporosis is a preventable disease, clinical testing for this and other polymorphisms may have a future role to play in the clinical assessment of osteoporotic fracture risk, along with other diagnostic tools such as biochemical markers of bone turnover and bone densitometry.
遗传因素在骨质疏松症的发病机制中起着重要作用。骨质疏松症是一种常见病症，其特征为骨量减少和骨折风险增加。双胞胎和家族研究表明，骨矿物质密度高达85%的差异是由遗传决定的，分子遗传学研究已经确定了几个可能参与这一过程的候选基因。维生素D受体基因（VDR）得到了最广泛的研究，但VDR多态性与骨密度之间的关系并不一致，在不同人群中的重复性也很差。其他候选基因及其周围的多态性也与骨量有关，但迄今为止确定的最有前景的候选基因是1型胶原蛋白α基因。最近描述了该基因调控区域的一种多态性，它影响转录因子Sp1的一个识别位点。这种多态性不仅与骨量有关，还与骨质流失以及骨质疏松性骨折这一临床重要病症有关。由于骨质疏松症是一种可预防的疾病，对这种及其他多态性进行临床检测，连同骨转换生化标志物和骨密度测定等其他诊断工具一起，可能在骨质疏松性骨折风险的临床评估中发挥未来的作用。
