Longitudinal relationships of polycyclic aromatic hydrocarbons exposure and genetic susceptibility with blood lipid profiles

Abstract

Objective: We aim to analyze the effects of polycyclic aromatic hydrocarbons (PAHs) exposure and genetic predisposition on blood lipid through a longitudinal epidemiological study.

Methods: We enrolled 4,356 observations who participated at baseline (n = 2,435) and 6-year follow-up (n = 1,921) from Wuhan-Zhuhai cohort. Ten urinary PAHs metabolites and blood lipid (i.e., total cholesterol [TC], triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], and high-density lipoprotein cholesterol [HDL-C]) were measured at both baseline and follow-up. The polygenic risk scores (PRS) of blood lipid were constructed by the corresponding genome-wide association studies. Linear mixed models were fit to identify associations between urinary PAHs metabolites, blood lipid, and lipid-PRSs in the repeated-measure analysis. Besides, longitudinal relationships of blood lipid with urinary PAHs metabolites and respective lipid-PRSs were examined by using linear regression models.

Results: Compared with subjects who had persistently low urinary total hydroxyphenanthrene (ΣOHPh), those with persistently high levels had an average increase of 0.137 mmol/l for TC and 0.129 mmol/l for LDL-C over 6 years. Each 1-unit increase of TC-, TG-, LDL-C-, and HDL-C-specific PRS were associated with an average increase of 0.438 mmol/l for TC, 0.264 mmol/l for TG, 0.198 mmol/l for LDL-C, and 0.043 mmol/l for HDL-C over 6 years, respectively. Compared with subjects who had low genetic risk and persistently low ΣOHPh, subjects with high LDL-specific PRS and persistently high ΣOHPh had an average increase of 0.652 mmol/l for LDL-C.

Conclusions: Our results suggest that high-level ΣOHPh exposure is associated with an average increase of LDL-C over 6 years, and those relationships can be aggravated by a higher LDL-C-genetic risk. No significant relationships were observed between other PAHs metabolites (including hydroxynaphthalene, hydroxyfluorene, and hydroxypyrene) and blood lipid changes over 6 years. Our findings emphasize the importance of preventing PAHs exposure, particularly among those with a higher genetic predisposition of hyperlipidemia.

Keywords: Blood lipid; Genetic susceptibility; Polycyclic aromatic hydrocarbons; Polygenic risk scores.