Institute of Sports Medicine, Beijing Key Laboratory of Sports Injuries, Peking University Third Hospital, Beijing, P.R. China; Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
Gene. 2018 Jul 20;664:192-195. doi: 10.1016/j.gene.2018.04.020. Epub 2018 Apr 20.
Developmental dysplasia of the hip (DDH) is a common skeletal disorder whereby genetic factors play a role in etiology. Multiple genes have been reported to be associated with the occurrence of DDH. WISP3 gene was found to be a causative gene for progressive pseudorheumatoid dysplasia (PPD). Reports of WISP3 gene in association with DDH are lacking. We conducted a case-control candidate gene association study enrolling three hundred and eighty-six patients with radiology confirmed DDH and 558 healthy controls. Additional haplotype-analysis was conducted to find the significant haplotype for DDH. Five SNPs rs69306665 (upstream of WISP3), rs1022313 (WISP3), rs1230345 (WISP3), rs17073268 (WISP3) and rs10456877 (downstream of WISP3) were identified for association with DDH, showing significant difference of allele frequencies with similar odds ratio ranging from 0.71 to 0.77 (p < 0.01) between cases and controls. Two haplotypes were identified between cases and controls through haplotype analysis: AAAAA with an odds ratio of 0.76 (95% CI: 0.60-0.98, p = 0.032299) and GGCGG with an odds ratio of 1.67 (95% CI: 1.37-2.04, p = 3.67 ∗ 10). The results suggested WISP3 gene was associated with DDH in Chinese Han population. GGCGG haplotype might be a biomarker for DDH.
发育性髋关节发育不良(DDH)是一种常见的骨骼疾病,遗传因素在其发病机制中起作用。多个基因已被报道与 DDH 的发生有关。WISP3 基因被发现是进行性假类风湿性发育不良(PPD)的致病基因。关于 WISP3 基因与 DDH 相关的报道较少。我们进行了一项病例对照候选基因关联研究,纳入了 386 名经放射学证实的 DDH 患者和 558 名健康对照者。进行额外的单体型分析以发现与 DDH 相关的显著单体型。rs69306665(WISP3 上游)、rs1022313(WISP3)、rs1230345(WISP3)、rs17073268(WISP3)和 rs10456877(WISP3 下游)这 5 个 SNP 与 DDH 相关,等位基因频率存在显著差异,病例组和对照组之间的比值比相似,范围在 0.71 到 0.77(p<0.01)之间。通过单体型分析,在病例组和对照组之间确定了两种单体型:AAAAA 的比值比为 0.76(95%CI:0.60-0.98,p=0.032299)和 GGCGG 的比值比为 1.67(95%CI:1.37-2.04,p=3.67×10)。结果表明,WISP3 基因与中国汉族人群的 DDH 相关。GGCGG 单体型可能是 DDH 的生物标志物。