Ingvarsson T, Stefánsson S E, Hallgrímsdóttir I B, Frigge M L, Jónsson H, Gulcher J, Jónsson H, Ragnarsson J I, Lohmander L S, Stefánsson K
Central Hospital, Akureyri, Iceland.
Arthritis Rheum. 2000 Dec;43(12):2785-92. doi: 10.1002/1529-0131(200012)43:12<2785::AID-ANR19>3.0.CO;2-I.
To assess, in a population-wide study in Iceland, the genetic contribution to hip osteoarthritis (OA) leading to total hip replacement (THR).
Information from 2 population-based databases in Iceland was combined: a national registry of all THRs performed between 1972 and 1996, and a genealogy database of all available Icelandic genealogy records for the last 11 centuries. A genetic contribution to THR for OA was assessed by 1) identifying familial clusters of OA patients with THR, 2) applying the minimum founder test (MFT) to estimate the minimum number of ancestors ("founders") that would account for the genealogy of all 2,713 patients with THR for OA, compared with the average number of founders for control lists, 3) calculating an average pairwise kinship coefficient (KC) for the patient list and control lists, and 4) estimating the relative risk (RR) for THR among relatives of OA patients who have undergone the procedure. One thousand matched control lists, each the same size as the patient list, were created using the genealogy database.
A large number of familial clusters of patients with THR for OA were identified. The MFT showed that OA patients descended from fewer founders than did subjects in the control groups (P < 0.001). The average pairwise KC among patients with OA was greater than in the control population (P < 0.001). The RR for THR among siblings of OA patients was 3.05 (95% confidence interval 2.52-3.10).
This population-based study shows that Icelandic patients with hip replacement for OA are significantly more related to each other than are matched controls drawn from the Icelandic population. These findings support a significant genetic contribution to a common form of OA and encourage the search for genes conferring an increased susceptibility to OA.
在冰岛开展的一项全人群研究中,评估导致全髋关节置换术(THR)的髋关节骨关节炎(OA)的遗传贡献。
整合了冰岛两个基于人群的数据库中的信息:一个是1972年至1996年间所有全髋关节置换术的国家登记册,另一个是过去11个世纪所有可用冰岛族谱记录的族谱数据库。通过以下方式评估OA导致THR的遗传贡献:1)识别接受THR的OA患者的家族聚集情况;2)应用最小奠基者检验(MFT)来估计能够解释所有2713例因OA接受THR患者族谱的祖先(“奠基者”)的最小数量,并与对照列表的平均奠基者数量进行比较;3)计算患者列表和对照列表的平均成对亲缘系数(KC);4)估计接受该手术的OA患者亲属中THR的相对风险(RR)。使用族谱数据库创建了1000个匹配的对照列表,每个对照列表的大小与患者列表相同。
识别出大量因OA接受THR的患者家族聚集情况。MFT显示,OA患者的奠基者数量少于对照组受试者(P < 0.001)。OA患者的平均成对KC高于对照人群(P < 0.001)。OA患者兄弟姐妹中THR的RR为3.05(95%置信区间2.52 - 3.10)。
这项基于人群的研究表明,因OA进行髋关节置换的冰岛患者之间的亲缘关系明显高于从冰岛人群中抽取的匹配对照组。这些发现支持了一种常见形式的OA存在显著的遗传贡献,并鼓励寻找赋予OA易感性增加的基因。