Liu Kun, Tan Li-Jun, Wang Peng, Chen Xiang-Ding, Zhu Li-Hua, Zeng Qin, Hu Yuan, Deng Hong-Wen
Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China.
Physical Examination Department, Guangxi medical university First affiliated hospital, Nanning, Guangxi, China.
PLoS One. 2017 Apr 3;12(4):e0174808. doi: 10.1371/journal.pone.0174808. eCollection 2017.
Osteoporosis is characterized by increased bone loss and deterioration of bone microarchitecture, which will lead to reduced bone strength and increased risk of fragility fractures. Previous studies have identified many genetic loci associated with osteoporosis, but functional mechanisms underlying the associations have rarely been explored. In order to explore the potential molecular functional mechanisms underlying the associations for osteoporosis, we performed integrative analyses by using the publically available datasets and resources. We searched 128 identified osteoporosis associated SNPs (P<10-6), and 8 SNPs exert cis-regulation effects on 11 eQTL target genes. Among the 8 SNPs, 2 SNPs (RPL31 rs2278729 and LRP5 rs3736228) were confirmed to impact the expression of 3 genes (RPL31, CPT1A and MTL5) that were differentially expressed between human subjects of high BMD group and low BMD group. All of the functional evidence suggested the important functional mechanisms underlying the associations of the 2 SNPs (rs2278729 and rs3736228) and 3 genes (RPL31, CPT1A and MTL5) with osteoporosis. This study may provide novel insights into the functional mechanisms underlying the osteoporosis associated genetic variants, which will help us to comprehend the potential mechanisms underlying the genetic association for osteoporosis.
骨质疏松症的特征是骨质流失增加和骨微结构退化，这将导致骨强度降低和脆性骨折风险增加。以往的研究已经确定了许多与骨质疏松症相关的基因位点，但这些关联背后的功能机制很少被探讨。为了探索骨质疏松症关联背后潜在的分子功能机制，我们使用公开可用的数据集和资源进行了综合分析。我们搜索了128个已确定的与骨质疏松症相关的单核苷酸多态性（P<10-6），其中8个单核苷酸多态性对11个表达数量性状基因座（eQTL）靶基因发挥顺式调控作用。在这8个单核苷酸多态性中，2个单核苷酸多态性（核糖体蛋白L31基因rs2278729和低密度脂蛋白受体相关蛋白5基因rs3736228）被证实影响3个基因（核糖体蛋白L31、肉碱/有机阳离子转运体1A和甲基转移酶样蛋白5）的表达，这3个基因在高骨密度组和低骨密度组的人类受试者之间存在差异表达。所有这些功能证据都表明了这2个单核苷酸多态性（rs2278729和rs3736228）以及3个基因（核糖体蛋白L31、肉碱/有机阳离子转运体1A和甲基转移酶样蛋白5）与骨质疏松症关联背后的重要功能机制。本研究可能为骨质疏松症相关基因变异的功能机制提供新的见解，这将有助于我们理解骨质疏松症遗传关联背后的潜在机制。
