The genetic epidemiology of human primary osteoarthritis: current status
The genetic epidemiology of human primary osteoarthritis: current status
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DOI：
10.1017/s1462399405009257
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发表时间：
2005-05-23
影响因子：
6.2
通讯作者：
Loughlin, John
中科院分区：
文献类型：
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作者：
Loughlin, John
骨关节炎（OA）是一种常见的疾病，其特征是髋关节和膝关节等滑膜关节的软骨退化。在过去的10年里，对该病进行了大量的双胞胎、同胞风险和分离研究，这些研究揭示了以非孟德尔方式传播的主要遗传成分。因此，OA最适合于复杂的多因素常见疾病类别。随着遗传成分的建立，进行了全基因组连锁扫描，这些发现了几个基因组间隔可能窝藏OA易感性。在过去的几年里，这些间隔已经开始产生含有OA相关变异的基因。因此，这是一个非常令人兴奋的时期，在分子遗传学分析这种常见的疾病。到目前为止，与易感性有关的基因包括染色体2q11.2-q13处的白细胞介素1基因（IL 1）簇、2p24.1处的基质蛋白3基因（MATN 3）、16p12.1处的IL-4受体α链基因（IL 4 R）、2q32.1处的分泌型卷曲相关蛋白3基因（FRZB）、金属蛋白酶基因ADAM 12位于10q26.2，最近，asporin基因（ASPN）位于9q22.31。这些基因参与OA的证据对某些人来说比其他人更有说服力，其中IL 1和ASPN的关联是迄今为止最令人信服的。必须通过对其他队列进行基因分型来检测每个关联的准确性，并通过对来自不同种族背景的OA队列进行基因分型来评估其全球相关性。IL 1、IL 4 R、FRZB和ASPN的基因产物调节软骨软骨细胞的分化和存活，它们对软骨细胞的影响可能适合治疗干预。因此，最新的遗传学为新型OA治疗的开发提供了新的见解。
Osteoarthritis (OA) is a common disease characterised by the degeneration of the cartilage of synovial joints such as the hip and knee. In the past ten years a large number of twin-pair, sibling-risk and segregation studies have been conducted on the disease, and these have revealed a major genetic component that is transmitted in a nonmendelian manner. OA therefore fits best into the complex, multifactorial class of common diseases. With a genetic component established, genome-wide linkage scans were performed, and these uncovered several genomic intervals likely to harbour OA susceptibility. In the past few years these intervals have started to yield genes containing OA-associated variants. This is therefore a very exciting period in the molecular genetic analysis of this common disease. The genes that have so far been implicated in susceptibility include the interleukin 1 gene (IL1) cluster at chromosome 2q11.2-q13, the matrilin 3 gene (MATN3) at 2p24.1, the IL-4 receptor alpha-chain gene (IL4R) at 16p12.1, the secreted frizzled-related protein 3 gene (FRZB) at 2q32.1, the metalloproteinase gene ADAM12 at 10q26.2 and, most recently, the asporin gene (ASPN) at 9q22.31. The evidence for involvement of these genes in OA is more compelling for some than others, with the IL1 and ASPN associations being the most convincing to date. It is imperative that the veracity of each of the associations be tested by genotyping additional cohorts and that their global relevance be assessed by genotyping OA cohorts from different ethnic backgrounds. The gene products of IL1, IL4R, FRZB and ASPN regulate cartilage chondrocyte differentiation and survival, and their effects on the chondrocyte are potentially amenable to therapeutic intervention. The latest genetics is therefore providing new insights for the development of novel OA treatments.