The long noncoding RNA expression profiles of paroxysmal atrial fibrillation identified by microarray analysis.

BACKGROUND

Long noncoding RNAs (lncRNAs) represent a novel class of noncoding RNAs that are involved in a variety of biological processes and human diseases. Recent evidence suggested that lncRNAs were associated with cardiac disorders. However, the roles of lncRNAs in paroxysmal atrial fibrillation (PAF) remain elusive. The purpose of the present study was to identify differentially expressed lncRNAs in PAF and predict their potential functions.

METHODS

Between May 2014 and December 2015, a total of 67 patients, including 34 patients with PAF and 33 patients without PAF were recruited in this study. Of these participants, 3 PAF patients and 3 controls were used for the microarray analysis and a separate cohort (31 PAF patients and 30 controls) were used for further validation. LncRNA profiles in the leukocytes were detected by microarray.

RESULTS

A total of 2095 and 1584 differentially expressed lncRNAs and mRNAs, respectively, were identified between the PAF patients and controls. Four lncRNAs (uc002nvy.3, ENST00000561094, uc004aef.3, ENST00000559960) were randomly selected for quantitative real-time PCR (qRT-PCR) in a separate cohort, validating that ENST00000559960 was upregulated and uc004aef.3 was downregulated in the PAF patients. uc002nvy.3 and ENST00000561094 showed no significant difference between PAF and the controls. Multiple logistic analyses showed that ENST00000559960 (OR 1.47; 95% CI 1.09 to 2.00; P=0.01) and uc004aef.3 (OR 0.63; 95% CI 0.41 to 0.96; P=0.03) were independently associated with PAF. Receiver operating characteristic (ROC) curves analyses revealed that ENST00000559960 and uc004aef.3 were modest predictors of PAF. The area under the curve (AUC) was 0.67±0.07 (95% CI 0.54-0.81; P=0.02) for uc004aef.3 and 0.70±0.07 (95% CI 0.56-0.83; P<0.01) for ENST00000559960. Bioinformatic analyses (lncRNAs classification and subgroup, gene ontology analysis, pathway analysis and gene co-expression network construction) were performed for predicting the role of lncRNAs.

CONCLUSIONS

Our results demonstrated that lncRNA profiles were differentially expressed in the PAF leukocytes, and two lncRNAs (ENST00000559960 and uc004aef.3) may help in prediction of PAF. This motivates further investigation of the role of lncRNAs for PAF.