Relation between Methylmercury Exposure and Plasma Paraoxonase Activity in Inuit Adults from Nunavik

BACKGROUND Methylmercury (MeHg) exposure has been linked to an increased risk of coronary heart disease (CHD). Paraoxonase 1 (PON1), an enzyme located in the high-density-lipoprotein (HDL) fraction of blood lipids, may protect against CHD by metabolizing toxic oxidized lipids associated with low-density liproprotein and HDL. MeHg has been shown to inhibit PON1 activity in vitro, but this effect has not been studied in human populations. OBJECTIVES This study was conducted to determine whether blood mercury levels are linked to decreased plasma PON1 activities in Inuit people who are highly exposed to MeHg through their seafood-based diet. METHODS We measured plasma PON1 activity using a fluorogenic substrate and blood concentrations of mercury and selenium by inductively coupled plasma mass spectrometry in 896 Inuit adults. Sociodemographic, anthropometric, clinical, dietary, and lifestyle variables as well as PON1 gene variants (rs705379, rs662, rs854560) were considered as possible confounders or modifiers of the mercury-PON1 relation in multivariate analyses. RESULTS In a multiple regression model adjusted for age, HDL cholesterol levels, omega-3 fatty acid content of erythrocyte membranes, and PON1 variants, blood mercury concentrations were inversely associated with PON1 activities [β-coefficient = -0.063; 95% confidence interval (CI), -0.091 to -0.035; p < 0.001], whereas blood selenium concentrations were positively associated with PON1 activities (β-coefficient = 0.067; 95% CI, 0.045-0.088; p < 0.001). We found no interaction between blood mercury levels and PON1 genotypes. CONCLUSIONS Our results suggest that MeHg exposure exerts an inhibitory effect on PON1 activity, which seems to be offset by selenium intake.