Cooper G S, Umbach D M
Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
J Bone Miner Res. 1996 Dec;11(12):1841-9. doi: 10.1002/jbmr.5650111203.
Vitamin D receptor (VDR) polymorphisms have been strongly associated with bone mineral density (BMD) in some studies but not in others. We used a meta-analytic approach to assess quantitatively the association between VDR and BMD and to examine the influence of specific study characteristics (e.g., skeletal site, mean age of subjects, menopausal status) on the reported results. Sixteen papers published in peer-reviewed journals through July 1996 were included. We calculated the mean difference, percent difference, and effect size (mean difference divided by standard deviation), comparing BMD between homozygous genotypes. At the hip, BMD in the BB genotype was lower than in the bb genotype (mean difference, -0.02 g/cm2; percent difference, -2.4% and effect size -0.18; p = 0.032). At the spine, the mean difference was -0.03 g/cm2; percent difference, -2.5%; and effect size, -0.19; p = 0.062. At the distal radius, the VDR effect was estimated as the mean difference, -0.01 g/cm2; percent difference, -1.7%; and effect size, -0.16; p = 0.078. The spine measurements exhibited the greatest between- and within-study variability. The difference in hip BMD between genotypes was larger (i.e., a more negative number) among the younger women and seemed to decrease with increasing age. However, statistical evidence for 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 between VDR polymorphisms and BMD, our analyses gave similar results, although the overall effect estimates were smaller. In the combined data from 29 study groups, the BB genotype frequency was 17.2, 4.9, and 2.3% in studies of whites, blacks, and Asians, respectively. VDR polymorphisms represent one genetic factor affecting BMD, but further research into the mechanisms, clinical significance, and its relation between other genetic and environmental factors is needed.
在一些研究中，维生素D受体（VDR）基因多态性与骨矿物质密度（BMD）密切相关，但在另一些研究中却并非如此。我们采用荟萃分析方法，定量评估VDR与BMD之间的关联，并考察特定研究特征（如骨骼部位、受试者平均年龄、绝经状态）对报告结果的影响。纳入了截至1996年7月在同行评审期刊上发表的16篇论文。我们计算了纯合基因型之间BMD的平均差异、百分比差异和效应大小（平均差异除以标准差）。在髋部，BB基因型的BMD低于bb基因型（平均差异为-0.02g/cm²；百分比差异为-2.4%，效应大小为-0.18；p = 0.032）。在脊柱，平均差异为-0.03g/cm²；百分比差异为-2.5%；效应大小为-0.19；p = 0.062。在桡骨远端，VDR效应估计为平均差异-0.01g/cm²；百分比差异-1.7%；效应大小-0.16；p = 0.078。脊柱测量结果在研究间和研究内的变异性最大。年轻女性中基因型之间髋部BMD的差异更大（即负数更大），且似乎随着年龄增长而减小。然而，这一趋势的统计学证据较弱（p = 0.06）。来自脊柱和桡骨的数据未显示VDR效应与年龄有类似的相互作用。当我们剔除VDR基因多态性与BMD关联的首篇报告中的数据时，尽管总体效应估计值较小，但分析结果相似。在29个研究组的合并数据中，白人、黑人及亚洲人研究中BB基因型频率分别为17.2%、4.9%和2.3%。VDR基因多态性是影响BMD的一个遗传因素，但仍需进一步研究其机制、临床意义以及与其他遗传和环境因素之间的关系。
