Variation in the BMP2 Gene: Bone Mineral Density and Ultrasound in Young Adult and Elderly Women
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- McGuigan, F.E., Larzenius, E., Callreus, M. et al. Calcif Tissue Int (2007) 81: 254. doi:10.1007/s00223-007-9054-9
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Bone morphogenetic protein-2 (BMP2) plays a key role in bone formation and maintenance. Studies of polymorphisms within the gene in relation to bone mineral density (BMD) and fracture have been inconsistent. Our aim was to investigate associations between polymorphisms in the BMP2 gene and bone mass, fracture, and quantitative ultrasound (QUS) measures at different stages of skeletal development. Study subjects were participants of two population-based cohorts of Swedish women: the PEAK-25 cohort of young adult women aged 25 years (n = 993) and the OPRA cohort of elderly women aged 75 years (n = 1,001). We analyzed four single-nucleotide polymorphisms (SNPs) across the BMP2 gene including the Ser37Ala SNP previously identified in relation to BMD, QUS of the calcaneus, and, in the elderly women, fracture. BMP2 gene variations were associated with QUS of bone, independent of BMD, but only in the young women. Even after adjusting for confounding factors, SNP rs235754 in the 3′ region of the gene was significantly associated with the ultrasound parameters speed of sound (P = 0.003) and stiffness (P = 0.002). The 5′ SNP rs235710 showed trends for QUS parameters (P = 0.02–0.07). No association with BMP2 SNPs was observed in either cohort for either BMD or fracture. While further, more extensive genotyping across the gene is recommended, as we may not have captured all information, our preliminary data suggest that variation in BMP2 may play a previously unidentified role in aspects of bone quality, which may be age- and site-dependent.