Department of Epidemiology, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands.
Department of Internal Medicine, Erasmus University Medical Center, 's-Gravendijkwal 230, 3015 CE Rotterdam, the Netherlands.
Int J Mol Sci. 2017 Nov 25;18(12):2529. doi: 10.3390/ijms18122529.
MicroRNAs (miRNAs) are small non-coding RNA molecules that post-transcriptionally regulate the translation of messenger RNAs. Given the crucial role of miRNAs in gene expression, genetic variants within miRNA-related sequences may affect miRNA function and contribute to disease risk. Osteoporosis is characterized by reduced bone mass, and bone mineral density (BMD) is a major diagnostic proxy to assess osteoporosis risk. Here, we aimed to identify miRNAs that are involved in BMD using data from recent genome-wide association studies (GWAS) on femoral neck, lumbar spine and forearm BMD. Of 242 miRNA-variants available in the GWAS data, we found rs11614913:C > T in the precursor to be significantly associated with femoral neck-BMD (-value = 9.9 × 10, β = -0.038) and lumbar spine-BMD (-value = 3.2 × 10, β = -0.061). Furthermore, our sensitivity analyses using the Rotterdam study data showed a sex-specific association of rs11614913 with BMD only in women. Subsequently, we highlighted a number of target genes, expressed in bone and associated with BMD, that may mediate the miRNA function in BMD. Collectively, our results suggest that may contribute to variations in BMD level. Further biological investigations will give more insights into the mechanisms by which control expression of BMD-related genes.
微小 RNA（miRNAs）是一类小的非编码 RNA 分子，可在后转录水平调控信使 RNA 的翻译。鉴于 miRNAs 在基因表达中的关键作用，miRNA 相关序列中的遗传变异可能会影响 miRNA 的功能并导致疾病风险增加。骨质疏松症的特征是骨量减少，而骨矿物质密度（BMD）是评估骨质疏松症风险的主要诊断指标。在这里，我们旨在利用最近关于股骨颈、腰椎和前臂 BMD 的全基因组关联研究（GWAS）数据，鉴定参与 BMD 的 miRNAs。在 GWAS 数据中，我们发现 242 个 miRNA 变体中有 rs11614913：C>T 位于前体 miRNA 中，与股骨颈 BMD（-值=9.9×10，β=-0.038）和腰椎 BMD（-值=3.2×10，β=-0.061）显著相关。此外，我们使用 Rotterdam 研究数据进行的敏感性分析表明，rs11614913 仅在女性中与 BMD 存在性别特异性关联。随后，我们强调了一些在骨骼中表达并与 BMD 相关的靶基因，这些基因可能介导了 miRNA 在 BMD 中的功能。总的来说，我们的结果表明 可能导致 BMD 水平的变化。进一步的生物学研究将深入了解 控制 BMD 相关基因表达的机制。
