Question

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A genetic disposition to OA has been clear since it was first reported by Kellgren and coworkers [1] that generalized nodal OA was twice as likely to occur in first-degree relatives as in control individuals. Twin pair and family risk studies have indicated that there is a significantly higher concordance for OA between monozygotic twins than between dizygotic twins, and that the hereditable component of OA may be in the order of 50% to 65% [2]. However, because of theprevalence of OA in the general population and extensive clinical heterogeneity, the precise genetic contribution to the
pathogenesis of OA has been difficult to analyze. Moreover, it is clear that multiple genetic factors can contribute to the incidence and severity of OA, and that these may differ according to specific joint (hand, hip, knee, or spine), sex, and race. There is also evidence, given the variety of candidate genes that predispose to OA, that there may be an additive effect of individual genes in the development of disease [3].Several candidate genes encoding proteins of the extra-cellular matrix of the articular cartilage have been associated with early-onset OA [4]. In addition to point mutations in type II collagen [5], inherited forms of OA may be caused by muta- tions in several other genes that are expressed in cartilage,including those encoding types IV, V, and VI collagens, as
well as cartilage oligomeric matrix protein (COMP) [6].Candidate genes for OA have also been identified that are not structural proteins. Among such candidates are the secreted frizzled-related protein 3, asporin, and von Wille-brand factor genes [7,8]. In follow-up studies it has been reported that the asporin, frizzled-related protein 3, and von Willebrand factor genes have now been found not to replicate in large Caucasian meta-analyses and that the association with growth differentiation factor (GDF)-5 in Caucasians has been confirmed in larger meta-analyses [9-12]. Finally, evidence from mouse models indicates that genetic disorders affecting the architecture of subchondral bone can cause OA. Mice with a null mutation of the latent ADAMTS = a disintegrin and metalloprotease with thrombospondin motifs; CCR = C-C chemokine receptor; COMP = cartilage oligomeric matrix transforming growth factor (TGF)-binding protein-3, whichregulates the activation of TGF-, developed both osteo-sclerosis and OA [13]. In addition, a recent report demonstrated that a genetic defect of type I collagen resulted
in rapidly progressive OA in a mouse model [14].In recent population studies, genome-wide linkage scans have highlighted several specific genes involved in disease risk [15]. Chromosome 2q was positive in several scans,suggesting that this chromosome is likely to harbor one or more susceptibility genes.
不要机译，谢谢

Answer 1

骨关节炎的遗传倾向已明确，因为它是首先报道了Kellgren和同事
[1]：广义节点关节炎的两倍可能在一级亲属发生在控制个人。 一对双胞胎和家庭风险的研究表明，有一个显着较高的OA同卵双胞胎之间的一致性比异卵双胞胎之间，而OA的遗传的成分可能会在50％以65％。
[2]：然而，由于theprevalence的OA在一般人群和广泛的临床异质性，高精度遗传贡献OA的发病机制已难以分析。 此外，很显然，多种遗传因素可能导致关节炎的发生率和严重程度，而这些可能会有所不同根据具体的联合（手，髋关节，膝关节，或脊柱），性别和种族。 还有证据表明，由于候选基因品种易患关节炎，有可能是单个基因在疾病的发展，添加剂的效果。
[3]：几个候选基因的关节软骨细胞外基质蛋白编码已与早发性关节炎。
[4]：除了在第二型胶原蛋白基因点突变。
[5]：OA的形式可能是由遗传突变的系统蒸发散在其他几个基因的表达在软骨，包括编码类型四，五和六胶原蛋白，以及软骨造成寡聚基质蛋白（COMP）
[6]：对于OA的候选基因也已确定不属于结构蛋白。 在这些候选国是分泌型卷曲相关蛋白3，asporin，冯Wille的品牌因子基因。
[7,8]：在后续的研究中，有报道说，asporin，卷曲相关蛋白3，血管性血友病因子基因已经被发现是在大高加索复制荟萃分析，并与生长分化因子（GDF数据）-5协会高加索人已被证实在较大的荟萃分析。
[9-12]：最后，从小鼠模型的证据表明，影响软骨下骨结构遗传性疾病会导致关节炎。 趋化因子受体CCR的=;，与一个潜在的ADAMTS =一整合素和血小板图案金属蛋白酶与无效突变小鼠比赛=软骨寡聚基质转化生长因子（TGF） - 结合蛋白3，whichregulates中TGF -激活，开发既骨，硬化和OA 。
[13]：此外，最近的一份报告表明，一个基因缺陷型胶原在迅速进步的小鼠模型中，导致骨关节炎。
[14]：最近的人口研究，全基因组扫描连锁疾病的风险都强调参与。
[15]：几个特定的基因。 第二季度染色体阳性几次扫描，这表明这一染色体可能窝藏一个或多个易感基因。

Answer 2

遗传倾向于OA已经清楚,因为这是第一次报告和同事Kellgren[1]广义节点OA可能性为一般人的两倍一级亲属发生在作为在控制个人。双胞胎双和家庭风险的研究表明,有显著的更高的一致性之间办公双卵双生双胞胎之间,而非单卵双生子,hereditable组件的OA可能秩序的50%到65%[2]。然而,由于办公theprevalence一般人群及丰富的临床非均质性强、精确的基因的贡献的

发病机制的OA已经难以分析。此外,但可以肯定的是,多个遗传因素可以促进完整的发病率和严重程度,这些不同根据特定的联合(手、髋部、膝盖和脊柱)、性别、和种族都有关系。也有证据,并给出了各种各样的候选基因,办公自动化,易于加性效应可能有不同基因的疾病的发展[3]几种候选基因编码的蛋白质的细胞外基质关节软骨通常是办公自动化食欲[4]。除了II型胶原蛋白点突变,继承[5]的OA形式可能是由于muta——对其在其他几个基因,该基因表达,包括软骨编码类型4、5和6,空

oligomeric矩阵和软骨蛋白(找出)[6]候选基因办公也被发现,不是结构的蛋白质。在这样的候选人分泌的frizzled-related蛋白质3、asporin,·冯·Wille-brand基因因素[7、8]。在后续研究它有报道说,asporin,frizzled-related蛋白质第(三)项、·冯·手术基因因素已经发现在大的白人荟萃分析复制,协会生长分化因子(GDF)-在高加索人已经证实[12]大荟萃分析。最后,证据表明小鼠模型的体系结构影响基因疾病会导致骨关节软骨下骨以空突变小鼠的潜在ADAMTS = disintegrin和metalloprotease thrombospondin图案,与客户= 12 chemokine受体,找出=软骨oligomeric矩阵转化生长因子(TGF)——protein-3,whichregulates约束的活化,发达TGF——都osteo-sclerosis及营运[13]。此外,最近的一份报告显示基因缺陷I型胶原蛋白发生病变

在快速的进步在办公的老鼠模型[14]在最近的人口研究的基因组,突出了连锁扫描的基因在几个特殊疾病风险(15)。是积极的,能否做个概括的染色体在几个扫描,表明这种染色体可能携带一个或多个易患基因。