Centre de Recherche de l'Hôpital St-François d'Assise du Centre Hospitalier Universitaire de Québec, Quebec, Canada.
J Bone Miner Res. 2010 Apr;25(4):901-11. doi: 10.1359/jbmr.091014.
Osteoporosis is a bone disease characterized by low bone mineral density (BMD), a highly heritable polygenic trait. Women are more prone than men to develop osteoporosis owing to a lower peak bone mass and accelerated bone loss at menopause. Lack of estrogen thus is a major risk factor for osteoporosis. In addition to having strong similarity to the estrogen receptor 1 (ESR1), the orphan nuclear estrogen-related receptor gamma (ESRRgamma) is widely expressed and shows overlap with ESR1 expression in tissues where estrogen has important physiologic functions. For these reasons, we have undertaken a study of ESRRgamma sequence variants in association with bone measurements [heel quantitative ultrasound (QUS) by measurements of broadband ultrasound attenuation (BUA), speed of sound (SOS), and stiffness index (SI) and dual-energy X-ray absorptiometry (DXA) at the femoral neck (FN) and lumbar spine (LS)]. A silent variant was found to be associated with multiple bone measurements (LS, BUA, SOS, and SI), the p values ranging from .006 to .04 in a sample of 5144 Quebec women. The region of this variant was analyzed using the HapMap database and the Gabriel method to define a block of 20 kb. Using the Tagger method, eight TagSNPs were identified and genotyped in a sample of 1335 women. Four of these SNPs capture the five major block haplotypes. One SNP (rs2818964) and one haplotype were significantly associated with multiple bone measures. All SNPs involved in the associations were analyzed in two other sample sets with significant results in the same direction. These results suggest involvement of ESRRgamma in the determination of bone density in women.
骨质疏松症是一种以骨矿物质密度（BMD）低为特征的骨骼疾病，这是一种高度遗传的多基因特征。女性比男性更容易患上骨质疏松症，因为女性的峰值骨量较低，绝经后骨丢失加速。雌激素缺乏是骨质疏松症的主要危险因素。除了与雌激素受体 1（ESR1）具有很强的相似性外，孤儿核雌激素相关受体γ（ESRRγ）广泛表达，并与雌激素具有重要生理功能的组织中的 ESR1 表达重叠。基于这些原因，我们进行了一项关于 ESRRγ 序列变异与骨测量值（通过宽带超声衰减（BUA）、声速（SOS）和刚度指数（SI）的脚跟定量超声（QUS）以及股骨颈（FN）和腰椎（LS）的双能 X 射线吸收法（DXA））的关联研究。在一个包含 5144 名魁北克女性的样本中，发现一个沉默变异与多个骨骼测量值（LS、BUA、SOS 和 SI）相关，p 值范围从 0.006 到 0.04。使用 HapMap 数据库和 Gabriel 方法分析了该变体的区域，以定义一个 20kb 的块。使用 Tagger 方法，在一个包含 1335 名女性的样本中鉴定并分型了 8 个 TagSNP。这 8 个 SNP 中有 4 个捕获了 5 个主要的块单倍型。一个 SNP（rs2818964）和一个单倍型与多个骨骼指标显著相关。所有与关联相关的 SNP 都在另外两个样本集中进行了分析，结果方向一致，具有统计学意义。这些结果表明 ESRRγ 参与了女性骨密度的决定。
