Ralston S H
Department of Medicine and Therapeutics, University of Aberdeen, UK.
Scand J Clin Lab Invest Suppl. 1997;227:114-21.
Genetic factors play an important role in the pathogenesis of several bone diseases. The the most important of these is osteoporosis-a common condition characterised by reduced bone mass and increased fracture risk, which affects up to 40% of women and 12% of men at some point during life. Twin and family studies suggest that up to 85% of the variance in bone mineral density is genetically determined. Clinical 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 polymorphisms of the VDR and bone density has been found to be inconsistent and poorly reproducible in different populations. Polymorphisms in and around the genes encoding interleukin-6, tumour necrosis factor beta and the oestrogen receptor have also been associated with bone mass in some populations, but these have not been widely studied. In contrast, a functional polymorphism has been identified at a binding site for the transcription factor Sp1 in the collagen type I alpha I gene, which is associated with bone mass and osteoporotic fracture in several populations, suggesting that genotyping at this site may be of potential clinical value in the assessment of fracture risk. The importance of genetic factors in the regulation of bone mass, coupled with the ability to test for candidate polymorphisms in genomic DNA, indicates that genetic testing may play a role in the future assessment of osteoporotic fracture risk. The clinical value of this approach is at present unclear, but is likely to be an important area for future development as new polymorphisms are identified by genome wide searches and further analysis of candidate genes.
遗传因素在多种骨骼疾病的发病机制中起着重要作用。其中最重要的是骨质疏松症，这是一种常见病症，其特征是骨量减少和骨折风险增加，在一生中的某些时候，高达40%的女性和12%的男性会受到影响。双胞胎和家族研究表明，骨矿物质密度差异中高达85%是由遗传决定的。临床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，但在不同人群中，VDR多态性与骨密度之间的关系并不一致，且重现性较差。在一些人群中，编码白细胞介素-6、肿瘤坏死因子β和雌激素受体的基因及其周围的多态性也与骨量有关，但这些研究尚未广泛开展。相比之下，在I型胶原α1基因中已发现转录因子Sp1结合位点存在功能性多态性，在多个人群中，该多态性与骨量和骨质疏松性骨折相关，这表明在此位点进行基因分型在评估骨折风险方面可能具有潜在的临床价值。遗传因素在骨量调节中的重要性，加上能够检测基因组DNA中的候选多态性，表明基因检测可能在未来骨质疏松性骨折风险评估中发挥作用。目前这种方法的临床价值尚不清楚，但随着全基因组搜索和候选基因的进一步分析发现新的多态性，这可能是未来一个重要的发展领域。
