Molecular Evaluation of MicroRNA-146 Gene Variability (rs2910164 C> G) and its Association with Increased Susceptibility to Coronary Artery Disease

Abstract

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.

Keywords: Coronary Artery Disease (CAD); Hsa-miR-146a-5p; amplification refractory mutation system (ARMS-PCR); gene polymorphism; miRNA polymorphisms; microRNAs.