Longitudinal joint effects of polycyclic aromatic hydrocarbons exposure and genetic susceptibility on fasting plasma glucose: A prospective cohort study of general Chinese urban adults.

The effects of environmental polycyclic aromatic hydrocarbons (PAHs) exposure on glycemic regulation and the underlying genetic mechanism were still unclear. This study aimed to analyze the longitudinal joint effects of PAHs exposure and genetic susceptibility on fasting plasma glucose (FPG) through a longitudinal study. We included 4104 observations (2383 baseline participants and 1721 6-year follow-up participants) from Wuhan-Zhuhai cohort. Ten urinary PAHs metabolites and FPG were measured at both baseline and follow-up. We constructed the polygenic risk scores (PRS) of FPG from the corresponding genome-wide association studies. Linear mixed models were used to explore the associations of urinary PAHs metabolites or FPG-PRS on FPG levels in the repeated-measure analysis. Besides, the longitudinal relationships of urinary PAHs metabolites, FPG-PRS, and their joint effects on FPG change over 6 years were evaluated by linear regression models. Compared with participants with persistent low levels of urinary total PAHs metabolites, hydroxynaphthalene, and hydroxyphenanthrene, participants with persistent high levels had average decreases of 0.173, 0.188, and 0.263 mmol/L for FPG change over 6 years, respectively. Each 1-unit increase of FPG-PRS was associated with a 0.531 mmol/L for FPG change over 6 years. Besides, compared with participants with high FPG-PRS and persistent low levels of urinary total hydroxynaphthalene, hydroxyfluorene, and hydroxyphenanthrene, participants with low FPG-PRS and persistent high levels had average decreases of 0.322, 0.567, and 0.419 mmol/L for FPG change over 6 years. Our findings demonstrated that high-level PAHs exposure was longitudinally associated with an average decrease of FPG over 6 years, and low FPG genetic risk can enhance the above associations. Our findings emphasized the hypoglycemic effect of PAHs exposure, shed new light on the complex effects between PAHs exposure and genetic factors in the prevention of high FPG, and might provide some clues for the development of potential hypoglycemic agents.