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

Abstract

TPS 791: Occupational health 1, Exhibition Hall, Ground floor, August 26, 2019, 3:00 PM - 4:30 PM Aim: To evaluate the association between polycyclic aromatic hydrocarbon (PAH) related long non-coding RNAs (lncRNAs) and heart rate variability (HRV) indices in coke oven workers. Methods: A two-stage study was performed to identify lncRNAs associated with PAH exposures quantified using urinary monohydroxy-PAH metabolites and plasma benzo[a]pyrene-r-7, t-8,c-10-tetrahydrotetrol-albumin adducts. In discovery stage, we used Human 8X60k LncRNA Arrays to test different expression in plasma lncRNA between 12 exposed workers and 12 controls matching age, sex, and smoking. We validated associations with four selected lncRNAs in 403 coke oven workers by droplet digital polymerase chain reaction (the QX-200 system, Bio-Rad, Hercules, CA). Results: In the discovery stage, lncRNA expression profiles differed between the exposed and control groups, with 58 lncRNAs significantly down-regulated and 5 lncRNAs mildly up-regulated in the exposed group (fold change’s cutoff is 10 and false discovery rate <0.05). In the validation analysis, two lncRNAs were consistent with the chip results. In male, evaluated urinary1-hydroxynaphthalene and 2-hydroxyphenanthrene were significantly associated with lower ENST00000447277 expression (β=−0.200 and β=−0.286); while evaluated 2-hydroxyfluorene, total concentration of hydroxyfluorene, 2-hydroxyphenanthrene, total concentration of hydroxyphenanthrene and total concentration of all PAH metabolites were associated with lower NR_024564 expression (all P.< 0.05). These lncRNAs were associated with lower HRV. Moreover, the 2 lncRNAs were positively associated with the root mean of square of successive differences between adjacent normal NN intervals (β= 0.032 and β=0.036), and NR_024564 was positively related to high-frequency power (0.15 to 0.40 Hz) (β=0.077, all P< 0.05). However, in female, we only found increased urinary 4-hydroxyphenanthrene was related to lower ENST00000447277 expression (β=−0.145, P=0.034), and no significant association between ENST00000447277 and HRV. Conclusions: Associations of PAH exposures with lncRNA expression, and of lncRNA expression with HRV, suggested that lncRNAs might be a novel mechanism mediating the effects of PAH exposure on early cardiovascular damage.