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  • Title: The genetic polymorphisms of key genes in WNT pathway (LRP5 and AXIN1) was associated with osteoporosis susceptibility in Chinese Han population.
    Author: Cui Y, Hu X, Zhang C, Wang K.
    Journal: Endocrine; 2022 Feb; 75(2):560-574. PubMed ID: 34590211.
    Abstract:
    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 Ars2301522Crs9921222 could increase the susceptibility of osteoporosis (p = 0.026). The rs11228219LPR5, rs11228240 LPR5, rs2301522AXIN1, and rs9921222AXIN1 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.
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