A new discovery of genetic polymorphisms of important genes in WNT pathway (LPR5 and AXIN1) associated with osteoporosis susceptibility in Chinese Han population

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. LPR5 and AXIN1 play an important role in the classical Wnt/β-catenin signaling pathway. Our study was aimed to determine the association between 5 candidate single nucleotide polymorphisms (SNPs) of LPR5 or AXIN1 and osteoporosis susceptibility in Chinese Han population. Methods: the association analysis was conducted between 5 candidate SNPs and osteoporosis susceptibility among 1198 participants. Agena MassARRAY was used to genotype SNPs. The association between SNPs and osteoporosis susceptibility in different genetic models was analyzed by logistic regression analysis. Multi-factor dimension reduction (MDR) was used to analyze the interaction of SNP-SNP in the osteoporosis risk. The difference of clinical indicators under different genotypes was completed by one-way analysis of variance.Results: we found that LPR5 rs11228240, AXIN1 rs2301522 and rs9921222 were significantly associated with the osteoporosis susceptibility. The results of subgroup analysis showed that LPR5 rs11228240 (protective factor) and AXIN1 rs2301522 (risk factor) were significantly 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 results of Haplotype analysis showed that Ars2301522Crs9921222 could increase the susceptibility of osteoporosis. We also found that LRP5 rs11228219, AXIN1 rs2301522 and rs9921222 showed a potential association with some clinical indicators of osteoporosis.Conclusion: the SNPs of LPR5 and AXIN1 which are important genes in WNT classical pathway, have a potential association with osteoporosis susceptibility in Chinese Han population.