Essential metals modified the effects of polycyclic aromatic hydrocarbons on the metabolic syndrome: Mediation effects of miRNA

Metabolic syndrome (MetS) prevalence has increased dramatically worldwide and has become a public health issue. Polycyclic aromatic hydrocarbons (PAHs) were identified as risk factors of MetS, while essential metals are integral parts of metalloenzymes catalyzing metabolic processes. However, effects of co-exposure to PAHs and essential metals have not been investigated yet. We aimed to assess whether essential metals could modify the hazard effects of PAHs on MetS, and underlying mediation effects of microRNA (miRNAs) were further explored. A cross-sectional study of 1451 males including 278 MetS cases was conducted. Internal exposure levels of 5 classes of PAH metabolites, 7 essential metals, as well as expressions of PAHs-associated 8 plasma miRNAs were assessed. Multiple exposure models, Bayesian kernel machine regression (BKMR), and quantile g-computation (QGcomp) were used simultaneously to identify MetS-related critical chemicals. Mutual effect modification between chemicals and mediation effects of miRNAs on chemical-MetS association was testified. In this study, hydroxyphenanthrene (OHPhe) and selenium (Se) were consistently identified as MetS-related key chemicals in three statistical methods. OHPhe was positively associated with MetS [OR (95 % CI) = 1.79 (1.21, 2.65), P = 0.004], while Se had a negative relationship with MetS [OR (95 % CI) = 0.61 (0.43, 0.87), P = 0.007]. Effect modification analysis observed the association between OHPhe and MetS was weakened with increased Se exposure. Only the expression of miR-24-3p was negatively associated with MetS [OR (95 % CI) = 0.81 (0.66, 0.95), P = 0.048] and could mediate 16.1 % of OHPhe-MetS association in subjects with low Se exposure (≤0.87 μg/mmol creatinine) (P = 0.019). We found a mutual effect modification between OHPhe and Se on MetS, and the positive OHPhe-MetS association was attenuated with increased Se exposure. Mediation effects of miR-24-3p on OHPhe-MetS association were dependent on Se dose. Our findings may provide new insight into the prevention and intervention of MetS.