Shearman Amanda M, Karasik David, Gruenthal Kristen M, Demissie Serkalem, Cupples L Adrienne, Housman David E, Kiel Douglas P
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
J Bone Miner Res. 2004 May;19(5):773-81. doi: 10.1359/JBMR.0301258. Epub 2003 Dec 22.
ESR2 is expressed in bone cells, yet few studies have tested its variation for association with BMD, an important determinant of osteoporotic fractures. This was investigated in 723 men and 795 women from the Framingham study. Results show association of variation in this gene with BMD in both women and men.
Osteoporotic fracture risk is highly dependent on bone density, a quantitative multifactorial trait with a substantial genetic component. In contrast to the growing body of evidence that estrogen receptor alpha (ESR1) plays a role in bone metabolism, few studies have examined the estrogen receptor beta (ESR2) gene for association with BMD. An ESR2 CA repeat polymorphism, D14S1026, was associated with BMD in two small studies, each with <200 women.
The objective of this investigation was to assess whether D14S1026 or four other intronic polymorphisms were associated with BMD in 723 men and 795 women (mean age, 60 years) from the offspring cohort of the population-based Framingham Study. BMD was measured at the femur (neck, trochanter, and Ward's area) and the lumbar spine (L(2)-L(4)).
In both women and men, there was significant association of D14S1026 genotype with measures of femoral but not spinal BMD. In addition, genotypes of two common single nucleotide polymorphisms, rs1256031 and rs1256059, in strong linkage disequilibrium with one another but not with D14S1026, were associated with measures of femoral BMD in men. The rs1256031 genotypes had up to a 4.0% difference in mean femoral BMD. An inferred rs1256031-D14S1026-rs1256059 haplotype C-23CA-T was significantly associated with reduced femoral BMD in women (p = 0.03, 0.003, and 0.01 for neck, trochanter, and Ward's area, respectively). Haplotype-based BMD differences ranged from 3.0% to 4.3%.
We have observed significant association of common ESR2 variants with measures of femoral BMD in both men and women.
雌激素受体2（ESR2）在骨细胞中表达，但很少有研究检测其变异与骨密度（BMD）的关联，而骨密度是骨质疏松性骨折的一个重要决定因素。在弗雷明汉研究的723名男性和795名女性中对此进行了调查。结果显示该基因的变异在男性和女性中均与骨密度有关联。
骨质疏松性骨折风险高度依赖于骨密度，骨密度是一种具有大量遗传成分的定量多因素性状。与越来越多的证据表明雌激素受体α（ESR1）在骨代谢中起作用相反，很少有研究检测雌激素受体β（ESR2）基因与骨密度的关联。在两项小型研究中，每项研究的女性人数均少于200人，雌激素受体2的CA重复多态性D14S1026与骨密度有关联。
本研究的目的是评估在基于人群的弗雷明汉研究的子代队列中的723名男性和795名女性（平均年龄60岁）中，D14S1026或其他四个内含子多态性是否与骨密度有关联。在股骨（颈、转子和沃德三角区）和腰椎（L2-L4）测量骨密度。
在女性和男性中，D14S1026基因型与股骨骨密度测量值显著相关，但与脊柱骨密度无关。此外，两个常见单核苷酸多态性rs1256031和rs1256059的基因型彼此处于强连锁不平衡状态，但与D14S1026无关，它们与男性的股骨骨密度测量值相关。rs1256031基因型的平均股骨骨密度差异高达4.0%。一个推断的rs1256031-D14S1026-rs1256059单倍型C-23CA-T与女性股骨骨密度降低显著相关（分别在颈、转子和沃德三角区，p = 0.03、0.003和0.01）。基于单倍型的骨密度差异范围为3.0%至4.3%。
我们观察到常见的雌激素受体2变异在男性和女性中均与股骨骨密度测量值显著相关。
