Macdonald Helen M, McGuigan Fiona E, Stewart Alison, Black Alison J, Fraser William D, Ralston Stuart, Reid David M
Department of Medicine and Therapeutics, University of Aberdeen, Medical School Buildings, Foresterhill, Aberdeen, United Kingdom.
J Bone Miner Res. 2006 Jan;21(1):151-62. doi: 10.1359/JBMR.050906. Epub 2005 Sep 12.
The VDR is a candidate gene for osteoporosis. Here we studied five common polymorphisms of VDR in relation to calcium intake and vitamin D status in a population-based cohort of 3100 British women, but found no significant association with bone mass, bone loss, or fracture.
Population studies of vitamin D receptor (VDR) polymorphisms have produced conflicting results. We performed a comprehensive study dealing with all potential confounders in a large population to determine whether polymorphisms in the VDR gene influence bone health.
We studied 3100 women (50-63 years old) with bone markers, 25-hydroxyvitamin D, calcium, PTH, diet, and physical activity collected in 1998-2000. BMD was measured in 1990-1994 and 1998-2000. Fracture prevalence was assessed in 2002. Women were genotyped for five polymorphisms in the VDR gene: Cdx-2, Fok1, Bsm1, Apa1, and Taq1. The relationship between VDR and BMD, and interactions between VDR genotype, dietary calcium, and 25-hydroxyvitamin D, were examined using analysis of covariance.
Compared with carriers of the G allele, homozygotes for the rare Cdx-2 A polymorphism (n = 136) had less bone loss (-0.5 +/- 1.2 versus -0.7 +/- 1.0%/year [SD]; p = 0.01) and lower PTH (3.0 +/- 1.6 versus 3.4 +/- 2.0 pM; p = 0.03) despite similar vitamin D status. The association was not significant after correction for multiple testing or adjustment for confounders. At low calcium intakes, AA homozygotes had greater femoral neck (FN) BMD compared with carriers of the G allele, but at higher calcium intakes, the association was reversed. At low calcium intake, homozygotes for the b allele of Bsm1 had greater BMD compared with carriers of the B allele, but at higher calcium intakes, there was no difference. Similar results were seen for the Taq1 polymorphism. There was no evidence of gene-nutrient interaction when adjusted for body weight. No interactions between genotypes and vitamin D status on BMD were observed.
VDR does not seem to influence BMD or bone turnover in early postmenopausal white women with adequate calcium intake. Gene-nutrient interactions on BMD may be an indirect consequence of interactions between genotype and calcium intake on weight.
维生素D受体（VDR）是骨质疏松症的候选基因。在此，我们在一个基于人群的3100名英国女性队列中研究了VDR的五种常见多态性与钙摄入量和维生素D状态的关系，但未发现与骨量、骨质流失或骨折有显著关联。
维生素D受体（VDR）多态性的人群研究结果相互矛盾。我们进行了一项全面研究，处理了大量人群中的所有潜在混杂因素，以确定VDR基因中的多态性是否影响骨骼健康。
我们研究了3100名女性（50 - 63岁），她们在1998 - 2000年收集了骨标志物、25 - 羟基维生素D、钙、甲状旁腺激素、饮食和身体活动数据。1990 - 1994年和1998 - 2000年测量了骨密度。2002年评估了骨折患病率。对女性进行了VDR基因中五种多态性的基因分型：Cdx - 2、Fok1、Bsm1、Apa1和Taq1。使用协方差分析检查了VDR与骨密度之间的关系，以及VDR基因型、饮食钙和25 - 羟基维生素D之间的相互作用。
与G等位基因携带者相比，罕见的Cdx - 2 A多态性纯合子（n = 136）骨质流失较少（-0.5 ± 1.2与-0.7 ± 1.0%/年[标准差]；p = 0.01）且甲状旁腺激素水平较低（3.0 ± 1.6与3.4 ± 2.0 pM；p = 0.03），尽管维生素D状态相似。在进行多重检验校正或混杂因素调整后，该关联不显著。在低钙摄入量时，AA纯合子与G等位基因携带者相比，股骨颈（FN）骨密度更高，但在高钙摄入量时，这种关联则相反。在低钙摄入量时，Bsm1的b等位基因纯合子与B等位基因携带者相比，骨密度更高，但在高钙摄入量时，没有差异。Taq1多态性也观察到类似结果。调整体重后，没有基因 - 营养素相互作用的证据。未观察到基因型与维生素D状态对骨密度的相互作用。
在钙摄入量充足的绝经后早期白人女性中，VDR似乎不影响骨密度或骨转换。骨密度的基因 - 营养素相互作用可能是基因型与钙摄入量对体重相互作用的间接结果。
