Screening on platelet LncRNA expression profile discloses novel residual platelet reactivity biomarker.

Abstract

Double antiplatelet therapy (DAPT) has wide inter-individual variabilities in coronary heart disease (CHD) patients' responses, which undermines the prognosis effect in clinical practice. Long noncoding RNAs (lncRNAs) have been reported to be widely existed in platelets, albeit their potential roles in platelet responses to DAPT largely remains in the realm of the unknown. This study aims to screen differentially expressed lncRNAs responsible for high residual platelet reactivities under DAPT. We enrolled 144 CHD patients that received DAPT and assigned them to high platelet reactivity (HPR) group and baseline group according to their residual platelet reactivities. Statistical analysis and a series of experiments including microarray analysis, platelet reactivity screening, RNA isolation and lncRNA microarray analysis were explored to the research. We detected a total of 22,424 kinds of co-expressed lncRNAs in three pairs of patients between the HPR and baseline groups. We identified twenty differentially expressed lncRNAs and successfully validated three of them in the 144 patients. Ultimately, the expression of ensemble transcript ENST00000433442 was demonstrated as significantly correlated with high platelet reactivity (OR=0.487, P=.035) by logistic regression analysis. There is a considerable amount of lncRNAs in platelets, and the downregulated expression of ENST00000433442 is an independent risk factor for high residual platelet reactivity in CHD patients under DAPT.