Circulatory miRNAs as Novel Non-Invasive Biomarkers for the Diagnosis of Coronary Artery Disease in Patients with and Without Diabetes Mellitus

Abstract

MicroRNAs are short non-coding RNAs implicated in the negative regulation of candidate genes of various disease complications including coronary artery disease (CAD). Our study aims to identify the diagnostic potential of circulatory miR-133b and miR-21 in the pathophysiology of CAD and the effect of type-2 diabetes mellitus (T2DM) per se on their expression. A total of 132 subjects were recruited from Delhi and surrounding regions including 78 subjects with angiographically proven CAD with and without T2DM. Quantitative real-time PCR assays were carried out to measure the relative expression profiles of miRNAs. In this study, miR-133b was found to be significantly downregulated by 4.63 fold whereas, miR-21 was upregulated by 2.0 fold in plasma samples of CAD patients. Moreover, we found that the presence of T2DM in CAD patients substantially affected and deviated the expression of both the miRNAs in an opposing manner. miR-133b deviated from 4.94 to 3.91 fold whereas, miR-21 deviated from 2.04 to 1.82 fold. Furthermore, both the miRNAs exhibited significant diagnostic potential at optimum cut-off values with area under curve (AUC) of >79% as assessed by receiver operating characteristics (ROC) curve analysis. To the best of our knowledge, this is the first report from Indian population describing the significant differential expression profile of miR-133b and miR-21 in CAD patients suggesting their crucial role in the pathophysiology and individual’s susceptibility in developing CAD. We conclude that miR-133b and miR-21 can be considered as novel, non-invasive biomarkers in the diagnosis of CAD in the presence or absence of T2DM.