WNT 通路关键基因（LRP5 和 AXIN1）的遗传多态性与汉族人群骨质疏松症易感性相关。
The genetic polymorphisms of key genes in WNT pathway (LRP5 and AXIN1) was associated with osteoporosis susceptibility in Chinese Han population.
机构信息
Department of Orthopedics, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, China.
Department of Orthopedics, Ankang Central Hospital, Ankang, 725000, Shaanxi, China.
出版信息
Endocrine. 2022 Feb;75(2):560-574. doi: 10.1007/s12020-021-02866-z. Epub 2021 Sep 29.
BACKGROUND
Genetic factors play a critical role in the pathogenesis of osteoporosis. The imbalance of WNT/β-catenin will cause the occurrence of osteoporosis. LRP5 and AXIN1 play an important role in the classical Wnt/β-catenin signaling pathway. Our study was aimed to determine the association between five candidate single nucleotide polymorphisms (SNPs) of LRP5 or AXIN1 and osteoporosis susceptibility in Chinese Han population.
METHODS
A total of 599 osteoporosis patients and 599 healthy individuals were recruited for this case-control study. Agena MassARRAY was used to genotype SNPs. The association between SNPs and osteoporosis susceptibility in different genetic models was analyzed by PLINK software. We used false-positive report probability (FPRP) analysis to detect whether the positive results were just chance or noteworthy observations. Multifactor dimension reduction (MDR) was used to analyze the interaction of SNP-SNP in the osteoporosis risk. Finally, haplotype analysis was performed by plink1.07 and Haploview software.
RESULTS
We found that LRP5 rs11228240, AXIN1 rs2301522, and rs9921222 were significantly associated with the osteoporosis susceptibility. The results of subgroup analysis showed that LRP5 rs11228240 (protective factor) and AXIN1 rs2301522 (risk factor) were associated with the susceptibility of osteoporosis among participants who were age >60 years, female or BMI ≤ 24; AXIN1 rs9921222 significantly increased the risk of osteoporosis among participants with BMI ≤ 24. The genotype AC could increase the susceptibility of osteoporosis (p = 0.026). The rs11228219, rs11228240 , rs2301522, and rs9921222 four-site model was the best model for predicting the osteoporosis risk (test accuracy = 0.541; CVC = 10/10).
CONCLUSIONS
The LRP5-rs11228240, AXIN1-rs2301522, and AXIN1- rs9921222 were associated with osteoporosis susceptibility in Chinese Han population.
背景
遗传因素在骨质疏松症的发病机制中起着关键作用。WNT/β-catenin 的失衡会导致骨质疏松症的发生。LRP5 和 AXIN1 在经典 Wnt/β-catenin 信号通路中发挥重要作用。我们的研究旨在确定 LRP5 或 AXIN1 的五个候选单核苷酸多态性（SNP）与中国汉族人群骨质疏松症易感性之间的关联。
方法
本病例对照研究共纳入 599 例骨质疏松症患者和 599 例健康对照。采用 Agena MassARRAY 对 SNP 进行基因分型。PLINK 软件分析不同遗传模型下 SNP 与骨质疏松症易感性的关系。我们使用假阳性报告概率（FPRP）分析来检测阳性结果是否只是偶然或值得注意的观察结果。多因素降维（MDR）用于分析骨质疏松症风险中 SNP-SNP 的相互作用。最后，通过 plink1.07 和 Haploview 软件进行单体型分析。
结果
我们发现 LRP5 rs11228240、AXIN1 rs2301522 和 rs9921222 与骨质疏松症易感性显著相关。亚组分析结果显示，LRP5 rs11228240（保护因素）和 AXIN1 rs2301522（风险因素）与年龄>60 岁、女性或 BMI≤24 的参与者的骨质疏松症易感性相关；AXIN1 rs9921222 显著增加 BMI≤24 参与者的骨质疏松症风险。基因型 AC 可增加骨质疏松症的易感性（p=0.026）。rs11228219、rs11228240、rs2301522 和 rs9921222 四位点模型是预测骨质疏松症风险的最佳模型（测试准确性=0.541；CVC=10/10）。
结论
LRP5-rs11228240、AXIN1-rs2301522 和 AXIN1-rs9921222 与中国汉族人群骨质疏松症易感性相关。
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