Medical Centre of Orthopedics, The Second Hospital of Jilin University, Ziqiang Street No.218, Nanguan District, Changchun City, 130041, Jilin Province, China.
Gene Testing Centre of Changchun Tumor Hospital, Changchun City, 130012, Jilin Province, China.
Sci Rep. 2024 Mar 27;14(1):7301. doi: 10.1038/s41598-024-57929-8.
The genes of Wnt/β-catenin pathway may have potential roles in fat accumulation of Non-traumatic osteonecrosis of the femoral head (ONFH), but the effects of their variants in the pathway on ONFH development have been remained unclear. To explore the potential roles of the variants in the development of ONFH, we completed the investigation of the paired interactions as well as their related biological functions of 17 variants of GSK3β, LRP5, and FRP4 genes etc. in the pathway. The genotyping of the 17 variants were finished by MASS ARRAY PLATFORM in a 560 ONFH case-control system. The association of variants interactions with ONFH risk and clinical traits was evaluated by logistic regression analysis etc. and bioinformatics technology. The results showed that the genotype, allele frequency, and genetic models of Gsk3β rs334558 (G/A), SFRP4 rs1052981 (A/G), and LRP5 rs312778 (T/C) were significantly associated with the increased and decreased ONFH risk and clinical traits, respectively (P < 0.001-0.0002). Particularly, the paired interactions of six variants as well as eight variants also showed statistically increased and decreased ONFH risk, bilateral hip lesions risk and stage IV risk of ONFH, respectively (P < 0.044-0.004). Our results not only at the first time simultaneously showed exact serum lipid disorder and abnormal platelet function of ONFH in the same study system with the 17 variants polymorphisms of Wnt/β-catenin pathway but also shed light on the variants closely intervening the lipid disorder and abnormal coagulation of ONFH.
Wnt/β-catenin 通路的基因可能在非创伤性股骨头坏死（ONFH）的脂肪积累中具有潜在作用，但该通路中它们的变异对 ONFH 发展的影响仍不清楚。为了探讨这些变异在 ONFH 发展中的潜在作用，我们完成了对 GSK3β、LRP5 和 FRP4 等基因通路中 17 个变异的配对相互作用及其相关生物学功能的研究。通过 MASS ARRAY PLATFORM 在 560 例 ONFH 病例对照系统中完成了 17 个变异的基因分型。通过逻辑回归分析等生物信息学技术评估了变异相互作用与 ONFH 风险和临床特征的相关性。结果表明，Gsk3β rs334558（G/A）、SFRP4 rs1052981（A/G）和 LRP5 rs312778（T/C）的基因型、等位基因频率和遗传模型与增加和减少 ONFH 风险和临床特征分别显著相关（P < 0.001-0.0002）。特别是，六个变异和八个变异的配对相互作用也显示出统计学上增加和减少 ONFH 风险、双侧髋关节病变风险和 ONFH 第四阶段风险，分别（P < 0.044-0.004）。我们的研究结果不仅首次在同一研究系统中同时显示了确切的血清脂质紊乱和异常血小板功能，而且还揭示了与 ONFH 脂质紊乱和异常凝血密切相关的变异。
