miR-146 基因变异（rs2910164 C>G）的分子评估及其与冠心病易感性增加的关联。
Molecular Evaluation of MicroRNA-146 Gene Variability (rs2910164 C> G) and its Association with Increased Susceptibility to Coronary Artery Disease.
机构信息
Department of Medical Lab Technology, Faculty of Applied Medical Sciences, Prince Fahd Bin Sultan Research Chair, University of Tabuk, Tabuk, Saudi Arabia.
Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia.
出版信息
Microrna. 2020;9(5):363-372. doi: 10.2174/2211536609666201209151130.
AIM
Apart from the modifiable risk factors, genetic factors are believed to influence the outcome of Coronary Artery Diseases (CAD). Under the genetic factors, miRNA polymorphisms, namely Hsa-miR-146a-5p (rs2910164) have become an important tool to study the mechanism that underlies the pathogenesis of this disease. Therefore, we investigated the association of miR-146a gene variations with susceptibility of coronary artery diseases.
METHODOLOGY
This study was conducted on 100 CAD patients and 117 matched healthy individuals. Genotyping of the Hsa-miR-146a-5p C>G gene variation was performed by using Amplification Refractory Mutation System PCR method (ARMS-PCR).
RESULTS
The distribution of Hsa-miR-146a-5p rs2910164 C>G genotypes observed between patients and controls was significantly different (P=0.048). Moreover, the frequency of G allele (fG) was found to be significantly higher among patients than in controls (0.36 vs. 0.25). Our findings showed that the Hsa-miR-146a-5p C>G variant was associated with an increased risk of CAD in codominant inheritance model CC vs. CG genotype (OR = 1.84, 95% CI, 1.02-3.31; p=0.040) and (OR = 3.18, 95% CI, 1.02-9.9; p=0.045) for CC vs. GG genotype in dominant inheritance model. Whereas the G allele significantly increased the risk of coronary artery disease (OR =1,81, 95% CI, 1.18-2.78; p=0.006) compared to C allele. Taken together, these results demonstrated that miR-146a/rs2910164 is associated with susceptibility to coronary artery disease, providing novel insights into the genetic etiology and underlying biology of coronary artery disease.
CONCLUSION
Our findings indicated that Hsa-miR-146a-5p rs2910164 GG genotype and G allele are associated with increased susceptibility to Coronary Artery Disease. A larger sample size can be the key to progress in establishing the genetic co-relation of miRNA gene polymorphisms and cardiovascular diseases.
目的
除了可改变的风险因素外，遗传因素被认为会影响冠心病（CAD）的结果。在遗传因素中，miRNA 多态性，即 Hsa-miR-146a-5p（rs2910164）已成为研究该疾病发病机制的重要工具。因此，我们研究了 miR-146a 基因变异与冠心病易感性的关系。
方法
本研究纳入了 100 例 CAD 患者和 117 名匹配的健康个体。采用扩增受阻突变系统 PCR 法（ARMS-PCR）检测 Hsa-miR-146a-5p C>G 基因变异的基因型。
结果
患者和对照组之间观察到 Hsa-miR-146a-5p rs2910164 C>G 基因型的分布有显著差异（P=0.048）。此外，患者组 G 等位基因（fG）的频率明显高于对照组（0.36 比 0.25）。我们的研究结果表明，Hsa-miR-146a-5p C>G 变异与 CAD 的易感性相关，在共显性遗传模型 CC 与 CG 基因型中（OR=1.84，95%CI，1.02-3.31；p=0.040）和（OR=3.18，95%CI，1.02-9.9；p=0.045）CC 与 GG 基因型中，CC 基因型显著增加 CAD 的风险。而 G 等位基因与 C 等位基因相比，显著增加了冠心病的发病风险（OR=1.81，95%CI，1.18-2.78；p=0.006）。总之，这些结果表明 miR-146a/rs2910164 与冠心病的易感性相关，为冠心病的遗传病因学和潜在生物学提供了新的见解。
结论
我们的研究结果表明，Hsa-miR-146a-5p rs2910164 GG 基因型和 G 等位基因与冠心病的易感性增加有关。更大的样本量是确定 miRNA 基因多态性与心血管疾病遗传相关性的关键。
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