Association between polymorphisms in Wnt signaling pathway genes and bone mineral density in postmenopausal Korean women

Abstract

Objective: The purpose of this study was to investigate the association between single nucleotide polymorphisms in Wnt signal pathway genes and circulating osteoprotegerin (OPG), soluble receptor activator of the nuclear factor-kappa B ligand (sRANKL) levels, bone turnover markers, and bone mineral density (BMD) in postmenopausal Korean women. Methods: Wnt9a c256G>A; low-density lipoprotein receptor-related protein (LRP) 5 c266A>G, c2245C>G, c3893C>T, and c4099G>A; secreted frizzled-related protein (sFRP) 4 c1019G>A; axin II c148C>T and c1615G>A; glycogen synthase kinase binding protein (GBP) c455C>A; A-catenin c94G>T and c101G>T; T-cell factor 1 c663G>T, c734C>T, and c766G>A; and adenomatous polyposis coli c5465T>A polymorphisms were analyzed in 392 postmenopausal Korean women. Serum levels of OPG, sRANKL, and bone turnover markers were measured, and BMDs at the lumbar spine and femoral neck were examined. Results: Wnt9a c256G>A, LRP5 c2245C>G and c4099G>A, axin II c1615G>A, GBP c455C>A, A-catenin c94G>T and c101G>T, and T-cell factor 1 c663G>T and c734C>T single nucleotide polymorphisms were not observed. Among the genes showing polymorphisms, only the sFRP4 c1019G>A polymorphism was associated with BMD. The AA genotype in the sFRP4 c1019G>A polymorphism showed significantly lower lumbar spine BMD and a higher serum bone alkaline phosphatase level than did the GG genotype and showed a 6.39 times higher risk for osteoporosis at the lumbar spine compared with the GG genotype. No significant differences in bone turnover markers, OPG, and sRANKL were detected among the other single genotypes or the LRP haplotype genotype. Conclusions: Our results suggest that the sFRP4 c1019G>A polymorphism may be one of the genetic factors affecting lumbar spine BMD in postmenopausal Korean women.