Interaction between vitamin D receptor genotype and estrogen receptor α genotype influences vertebral fracture risk
Interaction between vitamin D receptor genotype and estrogen receptor α genotype influences vertebral fracture risk
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DOI：
10.1210/jc.2002-021861
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发表时间：
2003-08-01
影响因子：
5.8
通讯作者：
Pols, HAP
中科院分区：
文献类型：
--
作者：
Colin, EM;Uitterlinden, AG;Pols, HAP
鉴于维生素D与雌激素内分泌系统的相互作用，我们研究了雌激素受体(ER) α基因和维生素D受体（VDR）基因多态性对634名55岁及以上女性骨质疏松性椎体骨折易感性的联合影响。鉴定出BsmI、ApaI和TaqI限制性片段长度多态性的3个VDR单倍型（1、2和3）和PvuII和XbaI限制性片段长度多态性的3个er α单倍型（1、2和3）。在平均7年的随访期间，我们捕获了131例非椎体骨折病例和85例椎体骨折病例。erα单倍型1与椎体骨折风险增加呈剂量依赖性相关（P < 0.001），对应于风险等位基因每个拷贝的比值比为1.9[95%置信区间（CI）， 0.9-4.1]。VDR单倍型1在椎体骨折病例中被过度代表。ER α单倍型1与VDR单倍型1在决定椎体骨折风险方面存在显著交互作用（P = 0.01）。ER α单倍型1与椎体骨折风险的关联仅存在于VDR单倍型1的纯合携带者中。1型ER α单倍型杂合子的骨折风险为2.5 (95% CI, 0.6-9.9)，纯合子的骨折风险为10.3 （95% CI, 2.7-40）。这些关联与骨矿物质密度无关。总之，ER α和VDR基因多态性之间的相互作用导致女性骨质疏松性椎体骨折的风险增加，在很大程度上与骨密度无关。
In view of the interactions of vitamin D and the estrogen endocrine system, we studied the combined influence of polymorphisms in the estrogen receptor (ER) alpha gene and the vitamin D receptor (VDR) gene on the susceptibility to osteoporotic vertebral fractures in 634 women aged 55 yr and older. Three VDR haplotypes (1, 2, and 3) of the BsmI, ApaI, and TaqI restriction fragment length polymorphisms and three ERalpha haplotypes (1, 2, and 3) of the PvuII and XbaI restriction fragment length polymorphisms were identified. We captured 131 nonvertebral and 85 vertebral fracture cases during a mean follow-up period of 7 yr. ERalpha haplotype 1 was dose-dependently associated with increased vertebral fracture risk (P < 0.001) corresponding to an odds ratio of 1.9 [95% confidence interval (CI), 0.9-4.1] per copy of the risk allele. VDR haplotype 1 was overrepresented in vertebral fracture cases. There was a significant interaction (P = 0.01) between ER alpha haplotype 1 and VDR haplotype 1 in determining vertebral fracture risk. The association of ER alpha haplotype 1 with vertebral fracture risk was only present in homozygous carriers of VDR haplotype 1. The risk of fracture was 2.5 (95% CI, 0.6-9.9) for heterozygous and 10.3 (95% CI, 2.7-40) for homozygous carriers of ER alpha haplotype 1. These associations were independent of bone mineral density. In conclusion, interaction between ER alpha and VDR gene polymorphisms leads to increased risk of osteoporotic vertebral fractures in women, largely independent of bone mineral density.