Biochemistry Department, Pasteur Institute, Tehran, Iran.
Rheumatology Ward, Loghman Hospital, Shahid Beheshti Medical University (SBMU), Tehran, Iran.
Mutat Res Rev Mutat Res. 2020 Oct-Dec;786:108339. doi: 10.1016/j.mrrev.2020.108339. Epub 2020 Oct 13.
As a complex disease, osteoporosis is influenced by several genetic markers. Many studies have examined the link between the Sp1 binding site +1245 G > T (rs1800012) and -1997 G > T (rs1107946) variations in the COL1A1 gene with osteoporosis risk. However, the findings of these studies have been contradictory; therefore, we performed a meta-analysis to aggregate additional information and obtain increased statistical power to more efficiently estimate this correlation. A meta-analysis was conducted with studies published between 1991-2020 that were identified by a systematic electronic search of the Scopus and Clarivate Analytics databases. Studies with bone mineral density (BMD) data and complete genotypes of the single-nucleotide variations (SNVs) for the overall and postmenopausal female population were included in this meta-analysis and analyzed using the R metaphor package. A relationship between rs1800012 and significantly decreased BMD values at the lumbar spine and femoral neck was found in individuals carrying the "ss" versus the "SS" genotype in the overall population according to a random effects model (p < 0.0001). Similar results were also found in the postmenopausal female population (p = 0.003 and 0.0002, respectively). Such findings might be an indication of increased osteoporosis risk in both studied groups in individuals with the "ss" genotype. Although no association was identified between the -1997 G > T and low BMD in the overall population, those individuals with the "GT" genotype showed a higher level of BMD than those with "GG" in the subgroup analysis (p = 0.007). To determine which transcription factor (TF) might bind to the -1997 G > T in COL1A1, 45 TFs were identified based on bioinformatics predictions. According to the GSE35958 microarray dataset, 16 of 45 TFs showed differential expression profiles in osteoporotic human mesenchymal stem cells relative to normal samples from elderly donors. By identifying candidate TFs for the -1997 G > T site, our study offers a new perspective for future research.
作为一种复杂的疾病，骨质疏松症受到多个遗传标记的影响。许多研究都探讨了 COL1A1 基因中的 Sp1 结合位点+1245 G > T(rs1800012)和-1997 G > T(rs1107946) 变异与骨质疏松症风险之间的联系。然而，这些研究的结果存在矛盾，因此，我们进行了一项荟萃分析，以汇总更多信息并获得更大的统计效力，从而更有效地估计这种相关性。这项荟萃分析纳入了 1991 年至 2020 年期间发表的研究，通过系统地在 Scopus 和 Clarivate Analytics 数据库中进行电子检索确定这些研究。本荟萃分析纳入了具有骨密度（BMD）数据和单核苷酸变异（SNV）完全基因型的研究，这些 SNV 针对总体人群和绝经后女性人群，采用 R 隐喻包进行分析。根据随机效应模型，在总体人群中，携带“ss”基因型的个体与携带“SS”基因型的个体相比，rs1800012 与腰椎和股骨颈的 BMD 值显著降低相关（p < 0.0001）。在绝经后女性人群中也发现了类似的结果（分别为 p = 0.003 和 0.0002）。这些发现可能表明，在研究的两个群体中，携带“ss”基因型的个体的骨质疏松症风险增加。尽管在总体人群中未发现-1997 G > T 与低 BMD 之间存在关联，但在亚组分析中，携带“GT”基因型的个体的 BMD 水平高于携带“GG”基因型的个体（p = 0.007）。为了确定哪种转录因子（TF）可能与 COL1A1 中的-1997 G > T 结合，根据生物信息学预测，确定了 45 个 TF。根据 GSE35958 微阵列数据集，在与老年供体的正常样本相比，在骨质疏松症人类间充质干细胞中，有 16 个 TF 显示出差异表达谱。通过鉴定-1997 G > T 位点的候选 TF，我们的研究为未来的研究提供了一个新的视角。
