发育性髋关节发育不良(DDH)是一种致病基因尚不明确的多基因病,之前研究报道了多个DDH易感基因，本课题组前期的全基因组关联研究(GWAS)明确了多个潜在的DDH易感基因，通过GWAS研究及后期II阶段验证，我们发现WIF1基因多态性位点rs3782499与DDH显著相关，同时，WIF1基因在DDH病人及对照的髋关节组织样本中存在显著的差异表达，而位点rs3782499基因型的不同能显著影响DDH病人髋关节组织WIF1基因的表达，这些结果提示我们WIF1基因可能是DDH的一个致病基因，而位点rs3782499可能是其功能位点。本研究计划通过rs3782499位点的功能研究及WIF1基因在DDH发病中的作用研究明确rs3782499位点的功能及WIF1基因在DDH致病中的作用机理,为DDH的临床早期诊断和防治提供新思路。

Developmental dysplasia of the hip (DDH) is a polygenic disease with still unclear disease-causing genes. Previous studies have reported multiple potential DDH susceptible genes. Our Genome-wide association study(GWAS) has also discovered several susceptible genes for DDH. Through our GWAS results and subsequent replication study, polymorphism rs3782499 was found significantly associated with DDH. Besides，significant difference of WIF1 gene expression in hip joint tissue was demonstrated between DDH patients and controls. Moreover, Patients with rs3782499 genotype AA have a significantly increased expression of WIF1 than those with GG, indicating that rs3782499 was a functional variant regulating the expression of WIF1 as a potential disease-causing gene for DDH. The purpose of this study is to complete research for the function of the variant rs3782499 and determine the disease-causing mechanism of WIF1 gene in DDH occurrence, and thus provide new insights for the early diagnosis and prevention of DDH.