Association of circular RNAs and environmental risk factors with coronary heart disease

Abstract

Background Coronary heart disease (CHD) is a complex disease caused by multi-factors and a major threat to human health. Circular RNAs (circRNAs) have critical roles in various biological processes and diseases. This study explores the independent role of circRNAs and their interaction with environmental factors in CHD. Methods A case–control study was conducted from March 2015 to September 2017 in Fuzhou, China. A total of 585 CHD patients and 585 gender- and age-matched healthy controls were enrolled. Questionnaire survey, health examination and molecular biology laboratory testing were conducted. Microarray technology and quantitative real-time polymerase chain reaction (PCR) were used to profile the expression levels of circRNAs. The area under the curve (AUC) of the receiver operating characteristic (ROC) was used to determine the diagnostic cut-offs. Multivariate logistic regression and multiplicative analysis were used to analyse the effects of environmental factors and hsa_circ_0008507, hsa_circ_0001946, hsa_circ_0000284 and hsa_circ_0125589 on CHD. Results The expression profile of circRNAs showed that 3423 circRNAs were differentially expressed at P < 0.05, but none pass multiple testing correction. qRT-PCR further confirmed the expression levels of hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 in peripheral blood leukocytes in CHD cases were higher than those in non-CHD subjects (All p < 0.05). Hsa_circ_0008507 (OR = 1.29; 95% CI: 1.11–1.50), hsa_circ_0001946 (OR = 1.20; 95% CI: 1.01–1.42) and hsa_circ_0000284 (OR = 2.05; 95% CI: 1.32–3.19) were independent risk factors for CHD after controlling other common environmental risk factors. The AUC for hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 was 0.75, 0.71 and 0.68, respectively. Compared with non-smoking individuals with low hsa_circ_0008507 expression, the smokers with high hsa_circ_0008507 expression showed the highest magnitude of OR in CHD risk. Additionally, a statistically significant multiplicative interaction was found between hsa_circ_0008507 and smoking for CHD. Conclusions Hsa_circ_0008507, hsa_circ_0001946 and hsa_circ_0000284 were closely related to the occurrence and development of CHD. The combination of smoking and high hsa_circ_0008507 expression causes the occurrence and development of CHD.

Knockdown of lncRNA ENST00000609755.1 Confers Protection Against Early oxLDL-Induced Coronary Heart Disease

“…greatly reduce the risk of complications arising from CHD, side-effects can greatly reduce quality of life (33). Evidence has shown that environmental factors, genomes, and epigenetics play crucial roles in it etiology (27). In this study, we confirmed that the elevated expression of lnc-MICALL2-2 is an independent risk factor for CHD after adjustment for environmental factors, and knockdown subsequently confers protection against early pathological processes of oxLDL-induced CHD.…”

“…LncRNA expression levels were calculated using the 2 − CT method. Supplementary Table 2 lists the primers used for qRT-PCR, similar research methods have been applied in previous studies (27,28).…”

Disease-Associated Circular RNAs: From Biology to Computational Identification

“…Second, circRNAs are also highly expressed in the heart [89] and are reported to play a role in cardiac remodeling [90], stress response [91], endothelial-to-mesenchymal transition [92], metabolism [93,94], immune tolerance [95], atrial fibrillation [96], and apoptosis [97]. Thus, these circRNAs are suggested to participate in heart diseases such as heart failure [91,97,98], ventricular septal defect [99], chronic heart disease [92,[100][101][102], alcoholic cardiomyopathy [93], and rheumatic heart disease [96]. In the lung, circRNAs have been found to be important in lung fibrosis [103], cell growth [104], cell migration and invasion [105][106][107][108], cancer tumorigenesis [109], and so on; thus, these circRNAs play a role in various lung-related diseases such as lung cancer [105,107,[110][111][112], lung injury [113], and pulmonary hypertension [114].…”

Circular RNAs in Sudden Cardiac Death Related Diseases: Novel Biomarker for Clinical and Forensic Diagnosis

“…Research about circRNAs as potential biomarker for CAD is constantly developing ( Table 2 ). A recent microarray study identified 3423 dysregulated circRNAs in five CAD patients and five matched healthy controls [ 48 ]. The expression levels of hsa_circ_0001946, hsa_circ_0008507 and hsa_circ_0000284 were significantly elevated in peripheral CAD blood leukocytes, consistent with their expressions in the peripheral blood, but exhibited significant differences in various populations.…”