Genetic variant of WIF1 gene is functionally associated with developmental dysplasia of the hip in Han Chinese population
Genetic variant of WIF1 gene is functionally associated with developmental dysplasia of the hip in Han Chinese population
复制标题
WIF1基因的遗传变异与中国汉族人群髋关节发育不良存在功能相关性
DOI：
10.1038/s41598-018-36532-8
复制
发表时间：
2019-01-22
影响因子：
4.6
通讯作者：
Zhang, Yijian
中科院分区：
文献类型：
--
作者：
Sun, Ye;You, Yongqing;Zhang, Yijian
发育性髋关节发育不良是一种常见的骨骼疾病。研究表明WIF 1基因在骨骼发育中起重要作用。本研究旨在揭示DDH与WIF 1基因的相关性。本研究对1573例DDH患者（586例）和987例健康对照者（987例）进行了两阶段病例对照候选基因关联研究。在所有样本中进行多态性rs3782499基因分型。比较患者和对照组髋关节组织中WIF 1表达的差异。比较不同基因型DDH患者中WIF 1的表达情况。在585例患者和987例对照的两阶段研究中，发现SNP rs3782499与DDH显著相关。等位基因频率（p = 4.37 * 10（-5））和基因型分布在隐性模型（AG + GG vs. AA）中存在显著差异。DDH患者WIF 1的表达明显高于对照组。rs3782499基因AA型患者WIF 1的表达显著高于GG型患者。结论：WIF 1基因rs3782499多态性是中国汉族人群DDH中WIF 1基因表达调控的功能性变异，可能是DDH早期诊断的潜在生物标志物。
Developmental dysplasia of the hip (DDH) is a common skeletal disorder. Studies have demonstrated a significant role of WIF1 gene in skeletal development. The present study was conducted to reveal the association between DDH and gene WIF1. A two-stage case-control candidate gene association study was conducted in total 1573 samples (586 DDH patients and 987 healthy controls) in this study. Polymorphism rs3782499 was genotyped in all samples. Difference of WIF1 expression in hip joint tissue was compared between the patients and the controls. WIF1 expression was compared among different genotypes in DDH patients. The SNP rs3782499 was found significantly associated with DDH in the two-stage study with 585 patients and 987 controls. There was a significant difference in allele frequency (p = 4.37 * 10(-5)) and genotype distribution in a recessive model (AG + GG vs. AA). DDH patients were found to have significantly higher WIF1 expression than controls. Moreover, Patients with rs3782499 genotype AA have a significantly increased expression of WIF1 than those with GG. To conclude, polymorphism rs3782499 of WIF1 gene is a functional variant regulating the expression of WIF1 in DDH in Chinese Han population, which might be a potential biomarker for the early diagnosis of DDH.