Vitamin D receptor gene polymorphisms and the risk of fractures in older women
Vitamin D receptor gene polymorphisms and the risk of fractures in older women
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DOI：
10.1359/jbmr.1999.14.10.1637
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发表时间：
1999-10-01
影响因子：
6.2
通讯作者：
Cummings, SR
中科院分区：
文献类型：
--
作者：
Ensrud, KE;Stone, K;Cummings, SR
维生素 D 受体基因多态性与骨矿物质密度之间的关联存在争议。维生素 D 受体基因型与骨折风险之间的关系尚不确定。为了确定维生素 D 受体多态性是否与老年女性髋部、脊椎和其他（非髋部、非脊椎）骨折的风险相关，我们对 9704 名 65 岁及以上社区居住女性进行了一项前瞻性研究，进行了病例队列研究。将首次发生髋部骨折 (n = 181)、椎骨骨折 (n = 127) 和其他骨折 (n = 223) 的女性的维生素 D 受体等位基因和基因型频率与从队列中随机选择的对照女性进行比较。女性髋部、椎骨和其他骨折分析的平均随访时间分别为 6.5 年、3.7 年和 5.4 年。维生素 D 受体多态性通过使用 TaqI 和 ApaI 限制性位点核酸内切酶消化的基因组 DNA 聚合酶链式反应扩增来确定。所有非椎体骨折均经 X 光报告证实；通过查看 X 射线胶片来验证髋部骨折。椎骨骨折是通过基线和平均 3.7 年后的侧脊柱 X 线摄影的形态测量来定义的。骨折病例与其各自的对照之间的等位基因或基因型频率没有差异。维生素 D 受体基因型（由 TaqI、ApaI 或 TaqI 和 ApaI 的组合定义）与髋部、椎骨或其他骨折的风险没有显着相关。例如，与具有 TT 基因型的女性参考组相比，具有 Tt 和 tt 基因型的女性具有相似的年龄和体重调整后的髋部骨折风险（风险比分别为 0.9，95% CI 0.6-1.3，和 0.8，95% CI 0.5-1.2）、脊柱骨折（比值比 1.1，95% CI） 0.7-1.8 和 0.7，95% CI 0.4-1.3），或其他骨骼部位（风险比分别为 1.0，95% CI 0.7-1.4 和 1.0，95% CI 0.7-1.5）。这些发现在其他分析中没有改变，包括根据年龄、种族血统、跟骨骨密度、膳食钙摄入量、钙补充剂的使用、维生素 D 补充剂的使用和口服雌激素的使用进行调整和分层的分析。我们得出结论，TaqI 和 ApaI 定义的维生素 D 受体多态性与老年女性骨折风险无关。我们的结果表明，测定这些维生素 D 受体多态性并不是预测老年女性骨折风险的临床有用测试。
The association between vitamin D receptor gene polypmorphisms and bone mineral density is controversial. The relationship between vitamin D receptor genotype and risk of fracture is uncertain. To determine whether vitamin D receptor polymorphisms were associated with the risk of hip, vertebral, and other (nonhip, nonvertebral) fractures in elderly women, we conducted a case-cohort study within a prospective study of 9704 community-dwelling women aged 65 years and older. Vitamin D receptor allele and genotype frequencies in women who experienced first incident hip (n = 181), vertebral (n = 127), and other (n = 223) fractures were compared with those of control women selected randomly from the cohort. Average length of follow-up was 6.5, 3.7, and 5.4 years for women in hip, vertebral, and other fracture analyse;, respectively. Vitamin D receptor polymorphisms were determined by polymerase chain reaction amplification of genomic DNA using TaqI and ApaI restriction site endonuclease digestion. All nonvertebral fractures were confirmed by X-ray reports; hip fractures were validated by review of X-ray films. Vertebral fractures were defined by morphometry using lateral spine radiography at baseline and an average of 3.7 years later. Allele or genotype frequencies did not differ between fracture cases and their respective controls. Vitamin D receptor genotype (defined by TaqI, ApaI, or the combination of TaqI and ApaI) was not significantly associated with the risk of hip, vertebral, or other fractures. For example, compared with the referent group of women with TT genotype, those with Tt and tt genotypes had similar age- and weight-adjusted risks of fracture at the hip (hazard ratios 0.9, 95% confidence interval [CI] 0.6-1.3, and 0.8, 95% CI 0.5-1.2, respectively), spine (odds ratios 1.1, 95% CI 0.7-1.8, and 0.7, 95% CI 0.4-1.3, respectively), or other skeletal site (hazard ratios 1.0, 95% CI 0.7-1.4, and 1.0, 95% CI 0.7-1.5, respectively). These findings were not altered in additional analyses including those adjusted for and stratified by age, ethnic ancestry, calcaneal bone density, dietary calcium intake, use of calcium supplements, use of vitamin D supplements, and oral estrogen use. We conclude that Vitamin D receptor polymorphisms defined by TaqI and ApaI are not associated,vith the risk of fracture in older women. Our results suggest that determination of these vitamin D receptor polymorphisms is not a clinically useful test for the prediction of fracture risk in elderly women.