Abstract
Genome-wide association studies have identified that the gene variants in Wnt signaling associate with bone mineral density and fracture risk but the effects of the variants on the development of osteonecrosis of the femoral head (ONFH) have been unclear. Here, we analyzed the polymorphisms of 4 variants in GSK3β and SFRP4 genes of Wnt signaling and their association with the development of ONFH through Mass ARRAY® platform in 200 ONFH patients and 177controls in Chinese population. Our results showed that the genotypes and allele frequencies of all variants detected in SFRP4 and GSK3β genes were not significantly different between patients and controls (p > 0.05); the correlation analysis between the 4 variants genotypes and gender, age at onset, etiological classification, unilateral or bilateral hip lesions, and clinical stages of ONFH, respectively, did not confirm significant association (p > 0.05) although age at onset in the minor homozygous(CC) carriers of SFRP4 rs1052981 (T/C) was a statistically younger tendency than that of the major homozygous (TT) or heterozygous (TC) of the SNP (p = 0.051); moreover, all haplotypes analyzed and their association with the clinical phenotypes of ONFH were also shown no statistical significance (p > 0.05).These results suggest that the 4 variants analyzed by this study in GSK3β and SFRP4 genes of Wnt signaling pathway are unlikely to be associated with susceptibility to ONFH.
Highlights
Wnt signaling pathway, as a crucial regulator of tissue homeostasis and remodeling, plays key roles in the transdifferentiation between osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMMSCs) [1,2]
BMMSCs are multipotent cells that can differentiate into adipocytes or osteocytes, and the functional changes of BMMSCs differentiation pathway may contribute to the pathogenesis of ONFH [13, 14]
Interactions associated with the differentiation pathway of BMMSCs that promote adipogenesis and repress osteogenesis are considered as the major factors leading to steroid-related ONFH [15]
Summary
As a crucial regulator of tissue homeostasis and remodeling, plays key roles in the transdifferentiation between osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMMSCs) [1,2]. Multiple gene variants have been proposed as the genetic risk factors of ONFH [7] but its molecular pathogenesis has been remained obscure. Genome-wide association studies (GWAS) have identified that common variants of genes in Wnt signaling associated closely with bone mineral density www.impactjournals.com/oncotarget (BMD) and risk of fracture, and several recent GWAS studies demonstrate that genetic variations in Wnt are correlated with BMD and risk of fracture in children and adults across multiple populations [9,10,11]. We analyzed the genotypes, allele, haplotype frequencies of 4 variants of glycogen synthase kinase 3 beta (GSK3β) and secreted frizzled-related protein 4 (SFRP4) genes in Wnt signaling and their association with the risk and clinical phenotypes of ONFH in 200 ONFH patients and 177controls in Chinese population
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