Single-nucleotide polymorphisms and haplotypes of bone morphogenetic protein genes and peripheral bone mineral density in young Korean men and women

Bone morphogenetic proteins (BMPs) play critical roles in osteoblast differentiation. To investigate the association between common single-nucleotide polymorphisms (SNPs) of BMPs and bone mineral density (BMD), a cross-sectional study was conducted in healthy Korean men (n = 237) and women (n = 276) aged 20-39 years. Calcaneus and distal radius BMD were measured by dual energy X-ray absorptiometry. SNPs of BMP2 (-1103C > A, c.584G > A, IVS1-2744A > G, c.893T > A), BMP4 (c.712T > C, IVS1-160C > T), and BMP6 (c.1283C > G, IVS4-6838A > G, IVS5 + 24C > T) were determined using the 5'-nuclease assay. Significant associations were observed between BMP2 c.584G > A, c.893T > A genotypes and male calcaneus as well as female distal radius BMD. Men with the BMP2 c.893 AA genotype had a 16% higher BMD at the calcaneus (P for trend = 0.014), whereas women with this genotype had a 7% lower BMD at the distal radius than the other genotypes (P for trend = 0.010). A significant association was also observed between BMP4 IVS1-160C > T and male calcaneus BMD (P for trend = 0.024). When the association between haplotypes and BMD was investigated, the AAGA haplotype of BMP2 was significantly associated with low bone mass in female distal radius (P for trend = 0.013). These results suggested that one or more SNPs of BMP2 and BMP4 are associated with peripheral BMD in Korean men and women. However, this association is dependent on anatomical sites and gender. Thus, larger studies with complete coverage of SNPs are needed in the future.