ARE VITAMIN-D-RECEPTOR POLYMORPHISMS ASSOCIATED WITH BONE-MINERAL DENSITY - A METAANALYSIS

Vitamin D receptor (VDR) polymorphisms have been strongly associated w ith bone mineral density (BMD) in some studies but not in others. We u sed a meta-analytic approach to assess quantitatively the association between VDR and BMD and to examine the influence of specific study cha racteristics (e.g., skeletal site, mean age of subjects, menopausal st atus) on the reported results. Sixteen papers published in peer-review ed journals through July 1996 were included. We calculated the mean di fference, percent difference, and effect size (mean difference divided by standard deviation), comparing BMD between homozygous genotypes. A t the hip, BMD in the BE genotype was lower than in the bb genotype (m ean difference, -0.02 g/cm(2); percent difference, -2.4%; and effect s ize -0.18; p = 0.032). At the spine, the mean difference was -0.03 g/c m(2); percent difference, -2.5%; and effect size, -0.19; p = 0.062. At the distal radius, the VDR effect was estimated as the mean differenc e, -0.01 g/cm(2); percent difference, -1.7%; and effect size, -0.16; p = 0.078. The spine measurements exhibited the greatest between- and w ithin-study variability. The difference in hip BMD between genotypes w as larger (i.e., a more negative number) among the younger women and s eemed to decrease with increasing age. However, statistical evidence f or this trend was weak (p = 0.06). Data from the spine and the radius showed no evidence of a comparable interaction of the VDR effect with age. When we omitted data from the first report of an association betw een VDR polymorphisms and BMD, our analyses gave similar results, alth ough the overall effect estimates were smaller. In the combined data f rom 29 study groups, the BE genotype frequency was 17.2, 4.9, and 2.3% in studies of whites, blacks, and Asians, respectively. VDR polymorph isms represent one genetic factor affecting BMD, but further research into the mechanisms, clinical significance, and its relation between o ther genetic and environmental factors is needed.