Choi J-Y, Shin C S, Hong Y-C, Kang D
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 110-799, South Korea.
Calcif Tissue Int. 2006 Apr;78(4):203-11. doi: 10.1007/s00223-005-0139-z. Epub 2006 Apr 13.
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.
骨形态发生蛋白（BMPs）在成骨细胞分化中起关键作用。为了研究BMPs常见单核苷酸多态性（SNPs）与骨密度（BMD）之间的关联，对20 - 39岁的健康韩国男性（n = 237）和女性（n = 276）进行了一项横断面研究。采用双能X线吸收法测量跟骨和桡骨远端的骨密度。使用5'-核酸酶分析法测定BMP2（-1103C > A、c.584G > A、IVS1-2744A > G、c.893T > A）、BMP4（c.712T > C、IVS1-160C > T）和BMP6（c.1283C > G、IVS4-6838A > G、IVS5 + 24C > T）的SNPs。观察到BMP2的c.584G > A、c.893T > A基因型与男性跟骨以及女性桡骨远端骨密度之间存在显著关联。携带BMP2 c.893 AA基因型的男性跟骨骨密度比其他基因型高16%（趋势P值 = 0.014），而携带该基因型的女性桡骨远端骨密度比其他基因型低7%（趋势P值 = 0.010）。还观察到BMP4的IVS1-160C > T与男性跟骨骨密度之间存在显著关联（趋势P值 = 0.024）。在研究单倍型与骨密度之间的关联时，BMP2的AAGA单倍型与女性桡骨远端低骨量显著相关（趋势P值 = 0.013）。这些结果表明，BMP2和BMP4的一个或多个SNPs与韩国男性和女性的外周骨密度相关。然而，这种关联取决于解剖部位和性别。因此，未来需要进行覆盖所有SNPs的更大规模研究。
