Symposium on 'genetic polymorphisms and disease risk' - Genetics of osteoporosis
Symposium on 'genetic polymorphisms and disease risk' - Genetics of osteoporosis
复制标题
DOI：
10.1017/s002966510700540x
复制
发表时间：
2007-05-01
影响因子：
7
通讯作者：
Ralston, Stuart H.
中科院分区：
文献类型：
--
作者：
Ralston, Stuart H.
骨质疏松症是一种常见的疾病，具有很强的遗传成分，其特征是骨量减少和脆性骨折风险增加。双胞胎和家庭研究表明，遗传因素通过影响骨矿物质密度（BMD）和其他与骨折风险相关的表型而导致骨质疏松症，尽管骨折本身的遗传性是适度的。连锁研究已经确定了几个数量性状基因座，调节骨密度，但大多数致病基因仍有待确定。与此相反，单基因骨疾病的连锁研究已成功地在基因鉴定，并在许多这些基因的多态性已被发现有助于调节骨量在正常人群中。以人群为基础的研究已经确定了与骨量或骨质疏松性骨折相关的几个候选基因的多态性，尽管这些多态性仅占BMD调节的少量遗传贡献。环境因素，如饮食和体力活动也是BMD的重要决定因素，在某些情况下，已发现特定的营养素与遗传多态性相互作用，以调节BMD。从临床的角度来看，骨质疏松症的遗传基础知识的进步可能是重要的，在增加疾病的病理生理学的理解，提供新的遗传标记，以评估骨折的风险，并在确定基因和途径，形成分子靶点的设计下一代的药物治疗。
Osteoporosis is a common disease with a strong genetic component characterised by reduced bone mass and an increased risk of fragility fractures. Twin and family studies have shown that genetic factors contribute to osteoporosis by influencing bone mineral density (BMD), and other phenotypes that are associated with fracture risk, although the heritability of fracture itself is modest. Linkage studies have identified several quantitative trait loci that regulate BMD but most causal genes remain to be identified. In contrast, linkage studies in monogenic bone diseases have been successful in gene identification, and polymorphisms in many of these genes have been found to contribute to the regulation of bone mass in the normal population. Population-based studies have identified polymorphisms in several candidate genes that have been associated with bone mass or osteoporotic fracture, although individually these polymorphisms only account for a small amount of the genetic contribution to BMD regulation. Environmental factors such as diet and physical activity are also important determinants of BMD, and in some cases specific nutrients have been found to interact with genetic polymorphisms to regulate BMD. From a clinical standpoint, advances in knowledge about the genetic basis of osteoporosis are likely to be important in increasing the understanding of the pathophysiology of the disease; providing new genetic markers with which to assess fracture risk and in identifying genes and pathways that form molecular targets for the design of the next generation of drug treatments.