Ikegawa Shiro
Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, Tokyo, Japan.
Curr Opin Rheumatol. 2007 Sep;19(5):429-34. doi: 10.1097/BOR.0b013e32825b079d.
Osteoarthritis is a serious medical, social and economic problem affecting populations worldwide. Identifying susceptibility genes for osteoarthritis is a critical step in tackling this disease. The association study is today's most powerful tool for finding such genes, and the osteoarthritis research community has enjoyed initial success through the identification of several promising candidates. This review summarizes recent advances and emerging challenges in osteoarthritis association studies.
Replication studies have confirmed association of functional sequence variations in the secreted frizzled-related protein 3 (FRZB) and asporin (ASPN) genes with osteoarthritis. These studies have also prompted discussion of population-specific differences in reported associations. Association of several other promising genes with osteoarthritis, including LRCH1, RHOB, TXNDC3 and GDF5, await replication. The Human Genome Project and the International HapMap Project have established an infrastructure to support genome-wide association studies. Large-scale case-control association scans are underway, and genome-wide association scans are also beginning.
Due to initial success in confirming several susceptibility genes and the advent of the post-genome sequence era, this area of osteoarthritis study is expanding quickly. To overcome current challenges and to move on to the next stage, however, international collaboration based on a common platform is essential.
骨关节炎是一个严重的医学、社会和经济问题,影响着全球人群。确定骨关节炎的易感基因是攻克这一疾病的关键步骤。关联研究是目前寻找此类基因最有力的工具,骨关节炎研究界已通过鉴定出几个有前景的候选基因取得了初步成功。本综述总结了骨关节炎关联研究的最新进展和新出现的挑战。
重复研究已证实,分泌型卷曲相关蛋白3(FRZB)和抑瘤素(ASPN)基因的功能序列变异与骨关节炎相关。这些研究还引发了关于所报道关联中人群特异性差异的讨论。其他几个有前景的基因与骨关节炎的关联,包括LRCH1、RHOB、TXNDC3和GDF5,尚待重复验证。人类基因组计划和国际人类基因组单体型图计划已经建立了支持全基因组关联研究的基础设施。大规模病例对照关联扫描正在进行,全基因组关联扫描也已启动。
由于在确认几个易感基因方面取得了初步成功以及后基因组序列时代的到来,骨关节炎研究的这一领域正在迅速扩展。然而,要克服当前的挑战并进入下一阶段,基于共同平台的国际合作至关重要。