HIP JOINT REPLACEMENT FOR IDIOPATHIC OSTEOARTHRITIS AGGREGATES IN FAMILIES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 骨关节炎（OA）是一种多因素疾病。 环境、激素、肥胖、机械和遗传因素与其发病和进展有关。 OA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，并且可以与细微或明显的物理和/或放射学变化相关。 在骨、软骨和滑膜细胞和基质中观察到的组织学、生物化学和分子变化方面，OA也是异质性的。 为了确定OA引起的髋关节或膝关节衰竭是否有遗传因素，我们邀请接受髋关节或膝关节置换术治疗特发性OA的患者（先证者）提供关于其兄弟姐妹中需要关节置换的特发性OA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，我们使用美国流变学学会标准确诊特发性OA。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与配偶的兄弟姐妹中特发性OA关节成形术的患病率。在控制年龄和性别后，观察到髋关节置换术的家族聚集性，但膝关节置换术的家族聚集性，这表明终末期髋关节OA的遗传贡献，但不终末期膝关节OA。我们的结论是，在髋关节骨性关节炎患者中，识别导致关节衰竭的特发性骨性关节炎易感基因的尝试比膝关节骨性关节炎患者更有可能成功。

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.