Association of oestrogen receptor α gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone
Association of oestrogen receptor α gene polymorphisms with postmenopausal bone loss, bone mass, and quantitative ultrasound properties of bone
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DOI：
10.1136/jmg.2004.023895
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发表时间：
2005-03-01
影响因子：
4
通讯作者：
Ralston, SH
中科院分区：
文献类型：
--
作者：
Albagha, OME;Pettersson, U;Ralston, SH
背景资料：编码雌激素受体α（ESR 1）的基因似乎调节骨密度（BMD）和骨质疏松性骨折风险的其他决定因素。目的：在3054名苏格兰妇女的人群队列中研究ESR 1基因常见多态性和单倍型与骨质疏松症相关表型之间的关系。在ESR 1基因内含子1内的PvuII和XbaI限制性片段长度多态性定义的共同单倍型“px”，未接受激素替代治疗的绝经后妇女的股骨颈骨丢失（n=945; p=0.009）。与不携带px单倍型的受试者相比，携带一个px拷贝的受试者股骨颈骨丢失的年发生率高出14%，携带两个px拷贝的受试者高出22%。px单倍型与绝经后妇女股骨颈BMD较低相关（p=0.02），与整个研究人群跟骨宽带超声衰减（BUA）值降低相关（p=0.005）。在ESR 1启动子和任何表型研究的TA重复多态性之间没有关联，但在长程单倍型分析的TA重复的人数较少的人也进行了px单倍型有减少BUA values.Conclusions：ESR 1 px单倍型与减少髋关节BMD值和增加绝经后妇女股骨颈骨丢失率。与BUA的关联可能解释了ESR 1内含子1等位基因通过部分独立于BMD差异的机制预测骨质疏松性骨折的事实。
Background: The gene encoding oestrogen receptor alpha (ESR1) appears to regulate bone mineral density (BMD) and other determinants of osteoporotic fracture risk.Objective: To investigate the relation between common polymorphisms and haplotypes of the ESR1 gene and osteoporosis related phenotypes in a population based cohort of 3054 Scottish women.Results: There was a significant association between a common haplotype "px'', defined by the PvuII and XbaI restriction fragment length polymorphisms within intron 1 of the ESR1 gene, and femoral neck bone loss in postmenopausal women who had not received hormone replacement therapy (n=945; p=0.009). Annual rates of femoral neck bone loss were similar to14% higher in subjects who carried one copy of px and 22% higher in those who carried two copies, compared with those who did not carry the px haplotype. The px haplotype was associated with lower femoral neck BMD in the postmenopausal women (p=0.02), and with reduced calcaneal broadband ultrasound attenuation (BUA) values in the whole study population (p=0.005). There was no association between a TA repeat polymorphism in the ESR1 promoter and any phenotype studied, though on long range haplotype analysis subjects with a smaller number of TA repeats who also carried the px haplotype had reduced BUA values.Conclusions: The ESR1 px haplotype is associated with reduced hip BMD values and increased rates of femoral neck bone loss in postmenopausal women. An association with BUA may explain the fact that ESR1 intron 1 alleles predict osteoporotic fractures by a mechanism partly independent of differences in BMD.