Association of Polymorphisms of the Estrogen Receptor α Gene With Bone Mineral Density and Fracture Risk in Women: A Meta-Analysis
作者:John P. A. Ioannidis、Ioanna Stavrou、Thomas A. Trikalinos、Christos Zois、Maria Luisa Brandi、Luigi Gennari、Omar Albagha、Stuart H. Ralston、Agathocles Tsatsoulis
DOI:10.1359/jbmr.2002.17.11.2048
日期:——
The contribution of genetic polymorphisms to bone mineral density (BMD) and fracture risk in women is a controversial topic. We evaluated the effect of the XbaI and PvuII polymorphisms of the estrogen receptor α to BMD and fracture risk in a meta‐analysis, including published data and additional information from investigators. Five thousand eight hundred thirty‐four women from 30 study groups were analyzed with fixed and random effects models. The PvuII polymorphism was not associated with BMD at any skeletal site examined and 95% CIs exclude effects over 0.015 g/cm2 for both the femoral neck and the lumbar spine. Conversely, XX homozygotes (women carrying two copies of the gene variant without an XbaI restriction site) consistently had higher BMD than other subjects. The magnitude of the effect was similar in the femoral neck and lumbar spine (0.014 g/cm2 [95% CI, 0.003–0.025] and 0.015 g/cm2 [95% CI, 0.000–0.030], respectively; no between‐study heterogeneity for either). Total body BMD was also significantly higher in XX homozygotes (by 0.039 g/cm2 and 0.029 g/cm2 compared with Xx and xx, respectively). Available data on fractures suggested a protective effect for XX (odds ratio [OR], 0.66 [95% CI, 0.47–0.93] among 1591 women), but not PP (OR, 0.93 [95% CI, 0.72–1.18] among 2229 women). In summary, we have found that XX homozygotes may have higher BMD and also a decreased risk of fractures when compared with carriers of the x allele, whereas the PvuII polymorphism is not associated with either BMD or fracture risk.
遗传多态性对女性骨矿物质密度(BMD)和骨折风险的影响是一个有争议的话题。我们在一项荟萃分析中评估了雌激素受体α的 XbaI 和 PvuII 多态性对骨矿物质密度和骨折风险的影响,包括已发表的数据和研究者提供的其他信息。采用固定效应和随机效应模型对来自 30 个研究小组的 5834 名妇女进行了分析。在所研究的任何骨骼部位,PvuII 多态性都与 BMD 无关,股骨颈和腰椎的 95% CI 均排除了超过 0.015 g/cm2 的影响。相反,XX 同卵双生者(携带两个没有 XbaI 限制位点的基因变异拷贝的女性)的 BMD 始终高于其他受试者。股骨颈和腰椎的影响程度相似(分别为 0.014 g/cm2 [95% CI, 0.003-0.025] 和 0.015 g/cm2 [95% CI, 0.000-0.030] ;两者均无研究间异质性)。XX 同卵双生者的全身 BMD 也明显较高(与 Xx 和 xx 相比,分别增加了 0.039 g/cm2 和 0.029 g/cm2)。有关骨折的现有数据表明,XX 有保护作用(1591 名妇女的几率比 [OR],0.66 [95% CI,0.47-0.93]),但 PP 没有保护作用(2229 名妇女的几率比 [OR],0.93 [95% CI,0.72-1.18])。总之,我们发现,与 x 等位基因携带者相比,XX 同源基因携带者的 BMD 可能更高,骨折风险也更低,而 PvuII 多态性与 BMD 或骨折风险均无关。