Axe de Recherche en Santé des Populations et Environnementale, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Québec, QC, Canada.
Environ Health Perspect. 2011 Aug;119(8):1077-83. doi: 10.1289/ehp.1003296. Epub 2011 May 4.
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.
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.
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.
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.
Our results suggest that MeHg exposure exerts an inhibitory effect on PON1 activity, which seems to be offset by selenium intake.
甲基汞（MeHg）暴露与冠心病（CHD）风险增加有关。位于血液脂质高密度脂蛋白（HDL）部分的对氧磷酶 1（PON1），通过代谢与低密度脂蛋白和 HDL 相关的有毒氧化脂质，可能对 CHD 起到保护作用。已有研究表明，MeHg 可在体外抑制 PON1 活性，但尚未在人类人群中对此效应进行研究。
本研究旨在确定在因食用海鲜而高度暴露于 MeHg 的因纽特人群中，血液汞水平是否与血浆 PON1 活性降低有关。
我们使用荧光底物测量了 896 名因纽特成年人的血浆 PON1 活性，并通过电感耦合等离子体质谱法测量了血液中的汞和硒浓度。在多变量分析中，我们将社会人口统计学、人体测量学、临床、饮食和生活方式变量以及 PON1 基因变异（rs705379、rs662、rs854560）视为可能影响汞-PON1 关系的混杂因素或修饰因素。
在调整年龄、HDL 胆固醇水平、红细胞膜中 ω-3 脂肪酸含量和 PON1 变异的多元回归模型中，血液汞浓度与 PON1 活性呈负相关[β系数=-0.063；95%置信区间（CI）：-0.091 至-0.035；p<0.001]，而血液硒浓度与 PON1 活性呈正相关[β系数=0.067；95%CI：0.045-0.088；p<0.001]。我们未发现血液汞水平与 PON1 基因型之间存在交互作用。
我们的结果表明，MeHg 暴露对 PON1 活性产生抑制作用，而这种作用似乎被硒的摄入所抵消。
