Bastami Milad, Ghaderian Sayyed Mohamad Hossein, Omrani Mir Davood, Mirfakhraie Reza, Vakili Hossein, Parsa Saeed Alipour, Nariman-Saleh-Fam Ziba, Masotti Andrea
1 Medical Genetics Department, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran .
2 Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran .
Genet Test Mol Biomarkers. 2016 May;20(5):241-8. doi: 10.1089/gtmb.2015.0253. Epub 2016 Feb 24.
Recent studies have suggested that single-nucleotide polymorphisms (SNPs) in miRNA genes or their binding sites may alter an individual's susceptibility to coronary artery disease (CAD). In the present study, the association between two such SNPs (rs2910164 in miR-146a and rs12190287, which disrupts miRNA binding to TCF21) and CAD, in an Iranian population, was evaluated and in silico analyses were conducted to predict disease-related effects of miR-146a rs2910164.
The study population consisted of angiographically confirmed CAD patients (n = 300) and asymptomatic controls (n = 300). Genotyping was performed using the TaqMan genotyping assay.
A multivariate regression analysis revealed that rs2910164 was associated with an increased CAD risk in the dominant model. In comparison to GG homozygotes, individuals who carry at least one C allele had a significantly higher risk of CAD (GC+CC vs. GG, odds ratios [OR]: 1.82, 95% confidence intervals [CI]: 1.18-2.80, p = 6.358e-3). Similarly, TCF21 rs12190287 was observed to be associated with CAD in a log-additive model (OR: 0.63, 95% CI: 0.45-0.88, p = 6.584e-3). An in silico analysis revealed that rs2910164 may modify the miR-146a-3p-mediated regulation of several biological processes that are implicated in CAD, like those that are related to the regulation of apoptosis and immune response.
Our data provide the first evidence for the association of miR-146a rs2910164 and TCF21 rs12190287 with CAD in an Iranian population, encouraging further research to elucidate the disease-related effects of miR-146a rs2910164.
近期研究表明，微小RNA（miRNA）基因或其结合位点的单核苷酸多态性（SNP）可能会改变个体患冠状动脉疾病（CAD）的易感性。在本研究中，评估了伊朗人群中两个此类SNP（miR-146a中的rs2910164和破坏miRNA与TCF21结合的rs12190287）与CAD之间的关联，并进行了计算机模拟分析以预测miR-146a rs2910164与疾病相关的作用。
研究人群包括经血管造影证实的CAD患者（n = 300）和无症状对照者（n = 300）。使用TaqMan基因分型检测法进行基因分型。
多变量回归分析显示，在显性模型中rs2910164与CAD风险增加相关。与GG纯合子相比，携带至少一个C等位基因的个体患CAD的风险显著更高（GC + CC与GG相比，比值比[OR]：1.82，95%置信区间[CI]：1.18 - 2.80，p = 6.358e - 3）。同样，在对数加性模型中观察到TCF21 rs12190287与CAD相关（OR：0.63，95% CI：0.45 - 0.88，p = 6.584e - 3）。计算机模拟分析显示，rs2910164可能会改变miR - 146a - 3p介导的对几种与CAD相关的生物学过程的调控，如与细胞凋亡和免疫反应调控相关的过程。
我们的数据首次证明了在伊朗人群中miR - 146a rs2910164和TCF21 rs12190287与CAD相关，这鼓励进一步研究以阐明miR - 146a rs2910164与疾病相关的作用。
