Polymorphisms in the bone morphogenetic protein 2 (BMP2) gene do not affect bone mineral density in white men or women
Peak bone mineral density (BMD) achieved during adulthood is a major determinant of osteoporotic fracture in later life. Although environmental factors affect peak BMD, it is a highly heritable trait. Recently, bone morphogenetic protein 2 (BMP2) was reported as a susceptibility gene for osteoporotic fractures and low BMD in Icelandic and Danish populations.
To determine whether polymorphisms in the BMP2 gene contribute to BMD variation in our population of healthy American whites, we tested seven single nucleotide polymorphisms (SNPs), four of which were associated with osteoporotic phenotypes in the previous study. BMD at the femoral neck and lumbar spine (L2–L4) were measured by dual energy X-ray absorptiometry (DXA) in 411 men (age 18–61) and 1,291 pre-menopausal women (age 20–50). SNP genotypes/haplotypes were tested for population-based association with BMD using analysis of variance.
None of the polymorphisms tested reached statistical significance (all p values >0.05) for BMD at the femoral neck or lumbar spine in either gender. Two of the SNP haplotypes spanning the entire BMP2 gene were marginally associated with BMD in men (p values=0.019−0.043). However, these haplotypes would account for only a small, if any, portion of BMD variation and would not be significant after adjustment for multiple comparisons.
These results demonstrate that genetic variations in BMP2 do not substantially contribute to BMD variation in our population of healthy American whites.
KeywordsBone mineral density Bone morphogenetic protein 2 Genetic association Osteoporosis Single nucleotide polymorphism
We thank siblings and their parents who participated in this study, as well as the study coordinators, without whom this work would not have been possible. This work was supported by National Institutes of Health grants P01 AG–18397, R01 AR–43476, M01 RR–00750, and K24 AR–02095. SNP genotyping by MALDI-TOF mass spectrometry used the facilities of the Center for Medical Genomics at Indiana University School of Medicine, which is supported in part by a grant from the Indiana Genomics Initiative (INGEN). INGEN is supported in part by the Lilly Endowment, Inc. We thank Jinghua Zhao and Gayathri Rajan at the Center for Medical Genomics for their technical support on SNP genotyping.
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