Metabolic Bone Diseases and Genetic Research Unit (J.H., H.Zha., C.W., H.Y., W.H., J.G., W.F., Y.H., M.L., Y.L., H.Zhe., Zh.Z.), Department of Osteoporosis and Bone Diseases, and Department of Orthopedics (Ze.Z.), Shanghai Jiao Tong University Affiliated with Sixth People's Hospital 200233 Shanghai, China.
J Clin Endocrinol Metab. 2014 Apr;99(4):E665-73. doi: 10.1210/jc.2013-2086. Epub 2014 Jan 1.
The aims of this study were as follows: 1) to evaluate the association of serum sclerostin with bone mineral density (BMD) and markers of bone metabolism in postmenopausal Chinese women and 2) to observe the relationships of single-nucleotide polymorphisms (SNPs) within the sclerostin (SOST) gene with serum sclerostin, BMD, and markers of bone metabolism.
A cross-sectional study was conducted with 703 postmenopausal Chinese women. Ten tagging SNPs (rs1234612, rs1513670, rs1634330, rs1708635, rs2023794, rs7220711, rs74252774, rs851057, rs851058, and rs865429) of the SOST gene were genotyped. Serum sclerostin and markers of bone metabolism were measured, including serum intact PTH, 25-hydroxyvitamin D [25(OH)D], procollagen type 1 N-terminal propeptide, and β-CrossLaps of type I collagen containing cross-linked C-telopeptide (β-CTX). The BMD of the lumbar spine and proximal femur were measured by dual-energy X-ray absorptiometry.
Serum sclerostin was positively correlated with BMD at the lumbar spine, femoral neck, and total hip and with serum 25(OH)D (all P < .01) but negatively correlated with β-CTX (P < .01). The significant relationships between serum sclerostin and BMD and with serum β-CTX persisted, even after adjustments for age, body mass index, and serum 25(OH)D (all P < .01). However, there was no correlation between serum sclerostin and age or serum procollagen type 1 N-terminal propeptide. We failed to identify a significant association between the SNP, haplotypes of SOST and BMD, or serum sclerostin.
Our results suggested that serum sclerostin was positively correlated with the BMD at the lumbar spine, femoral neck, and total hip and with serum 25(OH)D but was negatively correlated with serum β-CTX. Genetic polymorphisms of SOST may not be a major contributor to variations in the serum sclerostin or BMD in postmenopausal Chinese women.
本研究的目的如下：1）评估绝经后中国女性血清骨硬化蛋白与骨密度（BMD）和骨代谢标志物的相关性；2）观察骨硬化蛋白（SOST）基因内单核苷酸多态性（SNP）与血清骨硬化蛋白、BMD 和骨代谢标志物的关系。
对 703 名绝经后中国女性进行了一项横断面研究。对 SOST 基因的 10 个标签 SNP（rs1234612、rs1513670、rs1634330、rs1708635、rs2023794、rs7220711、rs74252774、rs851057、rs851058 和 rs865429）进行了基因分型。测量了血清骨硬化蛋白和骨代谢标志物，包括血清完整甲状旁腺激素、25-羟维生素 D [25（OH）D]、I 型前胶原氨基端前肽和 β-胶原交联 C 端肽（β-CTX）。采用双能 X 线吸收法测量腰椎和股骨近端的 BMD。
血清骨硬化蛋白与腰椎、股骨颈和全髋 BMD 呈正相关，与血清 25（OH）D 呈正相关（均 P <.01），与 β-CTX 呈负相关（P <.01）。即使在调整年龄、体重指数和血清 25（OH）D 后，血清骨硬化蛋白与 BMD 及与血清 β-CTX 之间的显著关系仍然存在（均 P <.01）。然而，血清骨硬化蛋白与年龄或血清 I 型前胶原氨基端前肽之间无相关性。我们未能发现 SOST 基因 SNP、单倍型与 BMD 或血清骨硬化蛋白之间存在显著关联。
我们的结果表明，血清骨硬化蛋白与腰椎、股骨颈和全髋 BMD 呈正相关，与血清 25（OH）D 呈正相关，与血清 β-CTX 呈负相关。SOST 基因的遗传多态性可能不是绝经后中国女性血清骨硬化蛋白或 BMD 变异的主要原因。
