Division of Bone Diseases, Faculty of Medicine, Geneva University Hospitals, 1205, Geneva, Switzerland.
Department of Internal Medicine and Medical Disciplines, "Sapienza" University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
Osteoporos Int. 2018 Feb;29(2):339-346. doi: 10.1007/s00198-017-4272-0. Epub 2017 Oct 16.
We investigated the interaction between periostin SNPs and the SNPs of the genes assumed to modulate serum periostin levels and bone microstructure in a cohort of postmenopausal women. We identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels and on radial cortical porosity.
The purpose of this study is to investigate the interaction between periostin gene polymorphisms (SNPs) and other genes potentially responsible for modulating serum periostin levels and bone microstructure in a cohort of postmenopausal women.
In 648 postmenopausal women from the Geneva Retirees Cohort, we analyzed 6 periostin SNPs and another 149 SNPs in 14 genes, namely BMP2, CTNNB1, ESR1, ESR2, LRP5, LRP6, PTH, SPTBN1, SOST, TGFb1, TNFRSF11A, TNFSF11, TNFRSF11B and WNT16. Volumetric BMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography at the distal radius and tibia.
Serum periostin levels were associated with radial cortical porosity, including after adjustment for age, BMI, and years since menopause (p = 0.036). Sixteen SNPs in the ESR1, LRP5, TNFRSF11A, SOST, SPTBN1, TNFRSF11B and TNFSF11 genes were associated with serum periostin levels (p range 0.03-0.001) whereas 26 SNPs in 9 genes were associated with cortical porosity at the radius and/or at the tibia. WNT 16 was the gene with the highest number of SNPs associated with both trabecular and cortical microstructure. The periostin SNP rs9547970 was also associated with cortical porosity (p = 0.04). In particular, SNPs in LRP5, ESR1 and near the TNFRSF11A gene were associated with both cortical porosity and serum periostin levels. Eventually, we identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels (interaction p = 0.01) and on radial cortical porosity (interaction p = 0.005).
These results suggest that periostin expression is genetically modulated, particularly by polymorphisms in the Wnt pathway, and is thereby implicated in the genetic variation of bone microstructure.
本研究旨在探讨成纤维细胞生长因子 7 基因多态性（SNP）与其他可能调节绝经后妇女血清成纤维细胞生长因子 7 水平和骨微结构的基因 SNP 之间的相互作用。
在日内瓦退休人员队列的 648 名绝经后妇女中，我们分析了 6 个成纤维细胞生长因子 7 SNPs 和另外 149 个位于 14 个基因中的 SNPs，即 BMP2、CTNNB1、ESR1、ESR2、LRP5、LRP6、PTH、SPTBN1、SOST、TGFb1、TNFRSF11A、TNFSF11、TNFRSF11B 和 WNT16。通过高分辨率外周定量计算机断层扫描测量桡骨和胫骨远端的容积 BMD 和骨微结构。
血清成纤维细胞生长因子 7 水平与桡骨皮质孔隙率相关，包括调整年龄、BMI 和绝经后时间后的结果（p=0.036）。ESR1、LRP5、TNFRSF11A、SOST、SPTBN1、TNFRSF11B 和 TNFSF11 基因中的 16 个 SNPs 与血清成纤维细胞生长因子 7 水平相关（p 范围为 0.03-0.001），而 9 个基因中的 26 个 SNPs 与桡骨和/或胫骨皮质孔隙率相关。WNT16 是与骨小梁和皮质微结构均相关的 SNP 数量最多的基因。成纤维细胞生长因子 7 SNP rs9547970 也与皮质孔隙率相关（p=0.04）。特别是，LRP5、ESR1 和 TNFRSF11A 基因附近的 SNPs 与皮质孔隙率和血清成纤维细胞生长因子 7 水平均相关。最终，我们发现 LRP5 SNP rs648438 和成纤维细胞生长因子 7 SNP rs9547970 之间存在血清成纤维细胞生长因子 7 水平（交互作用 p=0.01）和桡骨皮质孔隙率（交互作用 p=0.005）的相互作用。
这些结果表明，成纤维细胞生长因子 7 的表达受到遗传调控，特别是受 Wnt 通路中多态性的调控，因此与骨微结构的遗传变异有关。
