Association of a single nucleotide polymorphism in the secreted frizzled-related protein 4 (sFRP4) gene with bone mineral density

Background: Wnt-β-catenin signaling pathway is involved in the regulation of bone mineral density (BMD). Secreted frizzled-related protein (sFRP) 4 that antagonize Wnt signals may modulate Wnt-β-catenin signaling pathway in the bone. Therefore, we analyzed expression of sFRP4 mRNA in primary osteoblasts and the association of a single nucleotide polymorphism (SNP) in the sFRP4 gene with BMD. Methods: Expression levels of sFRP4 mRNA were analyzed during the culture course of rat primary osteoblasts. Association of a SNP in the sFRP4 gene at Arg262 (CGC to CGT) with BMD was examined in 372 healthy post-menopausal Japanese women. Results: sFRP4 mRNA was detected and increased during the differentiation of rat primary osteoblasts. As an association study of the SNP in the sFRP4 gene, the subjects without the T allele (CC; n = 129) had significantly higher lumbar BMD than the subjects bearing at least one T allele (TT + CT; n = 243) (Z score; 0.054 versus−0.324; P = 0.0188). Conclusion: sFRP4 mRNA was expressed and regulated in primary osteoblasts. A genetic variation at the sFRP4 gene locus is associated with BMD, suggesting an involvement of sFRP4 gene in the bone metabolism.