Polycyclic aromatic hydrocarbons associated long non-coding RNAs and heart rate variability in coke oven workers

Epidemiological studies have showed that polycyclic aromatic hydrocarbons (PAHs) were associated with heart rate variability (HRV), but the role of long non-coding RNAs (lncRNAs) in the association is unknown. We aimed to identify PAHs-related lncRNAs and assess their associations with HRV among coke oven workers. Differential lncRNAs expression between 12 exposed workers and 12 controls was tested by Human 8X60k LncRNA Arrays in discovery stage, then selected NR_024564 was validated in 353 workers using droplet digital RT-PCR. Microarray results showed that 1234 lncRNAs were downregulated with 805 lncRNAs upregulated in exposed group (≥ 2-fold change). In validation stage, no significant association was observed between NR_024564 and PAH exposure or HRV in total subjects, while urinary 2-hydroxyfluorene (2-OHFlu) was inversely related to root mean square successive difference (RMSSD). However, in current smokers, NR_024564 was inversely related to urinary 2-OHFlu, 2-hydroxyphenanthrene, 1-hydroxypyrene (1-OHP), and total PAHs metabolites (ΣOH-PAHs), of which 1-OHP accounted for the strongest estimation for interaction with smoking status (P_interaction = 0.011). Also, the positive associations of NR_024564 with RMSSD and high frequency power showed an interaction with smoking status (P_interaction = 0.034 and 0.023, respectively). Also, urinary 2-OHFlu and ΣOH-PAHs were inversely associated with RMSSD in current smokers. In addition, elevated NR_024564 was dose-responsive related to increased RMSSD in above high-PAHs groups among smokers (all P_trend < 0.05). Our results revealed that NR_024564 and its interactions with smoking status might act as novel mechanisms regulating the adverse effects of PAHs on HRV.