Variation in the secreted frizzled-related protein-3 gene and risk of osteolysis and heterotopic ossification after total hip arthroplasty
Variation in the secreted frizzled-related protein-3 gene and risk of osteolysis and heterotopic ossification after total hip arthroplasty
复制标题
DOI：
10.1002/jor.20446
复制
发表时间：
2007-12-01
影响因子：
2.8
通讯作者：
Wilkinson, Jeremy Mark
中科院分区：
文献类型：
--
作者：
Gordon, Andrew;Southam, Lorraine;Wilkinson, Jeremy Mark
分泌型卷曲相关蛋白-3（sFRP 3）拮抗促进成人组织中新骨形成的配体。我们研究了编码sFRP 3的FRZB基因的变异是否与全髋关节置换术（THA）后骨质溶解或异位骨化（HO）的发生相关。从609名患者（骨质溶解组n = 268）中提取基因组DNA，平均11年后骨水泥THA治疗特发性骨关节炎，并对FRZB Arg 200 Trp和Arg 324 Gly多态性进行基因分型。Brooker分类用于评估563例受试者初次THA后的HO。骨质溶解受试者中FRZB 200 Trp等位基因的携带率为14.2%，对照组为21.0%（p 0.041）。该等位基因的携带率在HO受试者中为21.7%（n = 299），而在无HO受试者中为12.0%（p = 0.063）。在调整与骨质溶解或HO发生相关的其他风险因素的影响后，携带FRZB 200 Trp的骨质溶解的比值比为0.62（95%CI 0.38至0.99; p = 0.049），HO的比值比为1.64（1.05至2.54;p 0.028）。FRZB 324位点的变异与骨质溶解或HO无关。然而，最常见的单倍型（FRZB 200 Arg：324 Arg）与骨质溶解相关（OR 1.50，95%CI 1.09 - 2.07;p = 0.014）。我们的数据表明，FRZB Arg 200 Trp位点可能是THA后促成骨细胞活性的标志物。携带FRZB 200 Trp等位基因与“阳性”骨平衡表型（骨质溶解-：HO+）相关。(C)2007骨科研究学会。
Secreted frizzled-related protein-3 (sFRP3) antagonizes ligands that promote new bone formation in adult tissues. We examined whether variation in the FRZB gene that encodes sFRP3 is associated with development of osteolysis or heterotopic ossification (HO) after total hip arthroplasty (THA). Genomic DNA was extracted from 609 subjects (osteolysis group n = 268) at a mean of 11 years following cemented THA for idiopathic osteoarthritis and genotyped for the FRZB Arg200Trp and Arg324Gly polymorphisms. The Brooker classification was used to assess HO following primary THA in 563 of the subjects. The carriage rate of the FRZB 200Trp allele was 14.2% in subjects with osteolysis versus 21.0% in controls (p 0.041). The carriage rate of this allele was 21.7% in subjects with HO (n = 299) versus 12.0% in those without HO (p = 0.063). The odds ratio for osteolysis with carriage of FRZB 200Trp was 0.62 (95% CI 0.38 to 0.99; p = 0.049) and for HO was 1.64 (1.05 to 2.54;p 0.028), after adjustment for the effects of other risk factors associated with the development of osteolysis or HO. Variants in the FRZB 324 locus alone were not associated with osteolysis or HO. However, the most frequent haplotype (FRZB 200Arg:324Arg) was associated with osteolysis (OR 1.50,95% CI 1.09 to 2.07;p = 0.014). Our data suggest that the FRZB Arg200Trp locus may be a marker for pro-osteoblastic activity after THA. Carriage of the FRZB 200Trp allele is associated with a "positive" bone balance phenotype (osteolysis -: HO+). (C) 2007 Orthopaedic Research Society.