HIP JOINT REPLACEMENT FOR IDIOPATHIC OSTEOARTHRITIS AGGREGATES IN FAMILIES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 骨关节炎是一种多因素疾病。环境、激素、肥胖、机械和遗传因素与其发生和发展有关。骨性关节炎在临床上是异质性的，因为它可以影响大关节或小关节，可以是单关节或多关节，并可与细微或明显的物理和/或放射学改变相关。在骨、软骨、滑膜细胞和基质中观察到的组织学、生化和分子变化方面，骨关节炎也是异质性的。为了确定是否有遗传因素导致髋关节或膝关节衰竭，我们邀请了接受髋关节或膝关节置换术治疗特发性骨性关节炎的患者(先证者)提供关于其兄弟姐妹中需要关节置换术的特发性骨性关节炎患病率的详细家族史。我们还邀请他们的配偶提供关于他们兄弟姐妹的详细家族史，作为对照组。在先证者中，我们使用美国风湿病学会的标准确认了特发性骨性关节炎的诊断。队列包括635名接受全髋关节置换术的先证者的兄弟姐妹，486名接受全膝关节置换术的先证者的兄弟姐妹，以及787名配偶的兄弟姐妹。我们比较了先证者的兄弟姐妹和配偶的兄弟姐妹中特发性骨性关节炎的关节置换术的流行率。在控制了年龄和性别后，髋关节置换术的家族聚集性被观察到，但膝关节置换术的家族聚集性被观察到，这表明基因对终末期髋关节骨关节炎有贡献，但对终末期膝关节骨性关节炎没有遗传贡献。我们的结论是，试图识别导致关节衰竭的特发性骨性关节炎的易感基因，在髋部骨性关节炎患者中比在膝骨性骨性关节炎患者中更有可能成功。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Osteoarthritis (OA) is a multifactorial disease. Environmental, hormonal, obesity, mechanical, and genetic factors have been implicated in its onset and progression. OA is clinically heterogeneious because it can affect large or small joints, can be monoarticular or polyartiuclar, and can be associated with subtle or obvious physical and/or radiographic changes. OA is also heterogeneous with respect to the histologic, biochemical, and molecular changes observed in bone, cartilage, and synovial cells and matrices. In order to determine whether there is a genetic component to hip or knee joint failure due to OA, we invited patients (probands) undergoing hip or knee arthroplasty for management of idiopathic OA to provide detailed family histories regarding the prevalence of idiopathic OA requiring joint replacement in their siblings. We also invited their spouses to provide detailed family histories about their siblings to serve as a control group. In the probands, we confirmed the diagnosis of idiopathic OA using American College of Rheumatology criteria. The cohorts included the siblings of 635 probands undergoing total hip replacement, the siblings of 486 probands undergoing total knee replacement, and the siblings of 787 spouses. We compared the prevalence of arthroplasty for idiopathic OA among the siblings of the probands with that among the siblings of the spouses. Familial aggregation for hip arthroplasty, but not for knee arthroplasty, was observed after controlling for age and sex, suggesting a genetic contribution to end-stage hip OA but not to end-stage knee OA. We conclude that attempts to identify genes that predispose to idiopathic OA resulting in joint failure are more likely to be successful in patients with hip OA than in those with knee OA.