No association of the polymorphisms of the frizzled-related protein gene with peak bone mineral density in Chinese nuclear families

Abstract

Background: The Wnt/beta-catenin signaling pathway plays an important role in skeletal development. Polymorphisms of frizzled-related protein (FRZB), an antagonist of this pathway, may generate variations in bone mineral density (BMD). In this study, we analyzed the association between FRZB genotypes and peak BMD variation in the spines and hips of two relatively large samples of Chinese female-offspring and male-offspring nuclear families.

Methods: We recruited 1,260 subjects from 401 female-offspring nuclear families and 1,296 subjects from 427 male-offspring nuclear families and genotyped four tagging single nucleotide polymorphisms (tagSNPs) (rs6433993, rs409238, rs288324, and rs4666865) spanning the entire FRZB gene. The SNPs rs288326 and rs7775, which are associated with hip osteoarthritis, were not selected in this study because of their low minor allele frequencies (MAFs) in Chinese people. The quantitative transmission disequilibrium test (QTDT) was used to analyze the association between each SNP and haplotype with peak BMD in female- and male-offspring nuclear families.

Results: In the female-offspring nuclear families, we found no evidence of an association between either single SNPs or haplotypes and peak BMD in the spine or hip. In the male-offspring nuclear families, no within-family association was observed for either SNPs or haplotypes, although a significant total association was found between rs4666865 and spine BMD (P = 0.0299).

Conclusion: Our results suggest that natural variation in FRZB is not a major contributor to the observed variability in peak BMD in either Chinese females or males. Because ethnic differences in the FRZB genotypes may exist, other studies in different population are required to confirm such results.

Figure 1

Linkage disequilibrium (LD) patterns and haplotype frequencies for the FRZB gene. Block structures depicted by Haploview. The increasing degree of darkness of the cells from white to black represents the increasing strength of LD. The values in the cells are the pair-wise degrees of LD indicated by D' × 100 when D' < 1. In the figure, 1 to 4 represent rs6433993 rs409238 rs288324 and rs4666865 respectively. The haplotype frequency is denoted beside each corresponding haplotype and calculated from unrelated parents (n = 1602). a LD pattern for the FRZB gene. b Haplotype frequencies for the FRZB gene.