Drescher Olivia, Dewailly Eric, Diorio Caroline, Ouellet Nathalie, Sidi Elhadji Anassour Laouan, Abdous Belkacem, Valera Beatriz, Ayotte Pierre
Axe Santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec, QC, Canada.
1] Axe Santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec, QC, Canada [2] Département de médicine sociale et préventive, Université Laval, Québec, Quebec, Canada.
J Expo Sci Environ Epidemiol. 2014 Nov;24(6):608-14. doi: 10.1038/jes.2013.96. Epub 2014 Jan 22.
There is growing evidence that cardiovascular health can be affected by exposure to methylmercury (MeHg), by a mechanism involving oxidative stress. Paraoxonase 1 (PON1) is a high-density lipoprotein-bound enzyme that hydrolyzes toxic oxidized lipids and protects against cardiovascular diseases. Evidence from in vitro studies indicates that MeHg can inhibit PON1 activity but little is known regarding this effect in humans. We investigated whether increased blood mercury levels are associated with decreased serum PON1 activity in Cree people who are exposed to MeHg by fish consumption. We conducted a multi-community study of 881 Cree adults living in Eastern James Bay communities (Canada). Multivariate analyses considered sociodemographic, anthropometric, clinical, dietary and lifestyle variables and six PON1 gene variants (rs705379 (-108C/T), rs662 (Q192R), rs854560 (L55M), rs854572 (-909C/G), rs854571 (-832C/T) and rs705381 (-162C/T)). In a multiple regression model adjusted for all potential confounding factors and the rs854560 PON1 variant, a statistically significant MeHg*rs705379 interaction was observed. Blood mercury levels were inversely associated with serum PON1 activities in individual homozygous for the -108T allele (P=0.009). Our results suggest a gene-environment interaction between the rs705379 polymorphism and MeHg exposure on PON1 activity levels in this aboriginal population. This finding will need to be replicated in other population studies.
越来越多的证据表明，心血管健康可能会受到甲基汞（MeHg）暴露的影响，其机制涉及氧化应激。对氧磷酶1（PON1）是一种与高密度脂蛋白结合的酶，可水解有毒的氧化脂质并预防心血管疾病。体外研究的证据表明，甲基汞可抑制PON1活性，但对于这种效应在人类中的情况知之甚少。我们调查了通过食用鱼类接触甲基汞的克里族人群中，血液汞水平升高是否与血清PON1活性降低有关。我们对居住在加拿大东詹姆斯湾社区的881名克里族成年人进行了多社区研究。多变量分析考虑了社会人口统计学、人体测量学、临床、饮食和生活方式变量以及六个PON1基因变体（rs705379（-108C/T）、rs662（Q192R）、rs854560（L55M）、rs854572（-909C/G）、rs854571（-832C/T）和rs705381（-162C/T））。在一个针对所有潜在混杂因素和rs854560 PON1变体进行调整的多元回归模型中，观察到甲基汞*rs705379有统计学意义的相互作用。在-108T等位基因纯合个体中，血液汞水平与血清PON1活性呈负相关（P = 0.009）。我们的结果表明，在这个原住民群体中，rs705379多态性与甲基汞暴露之间在PON1活性水平上存在基因-环境相互作用。这一发现需要在其他人群研究中得到重复验证。
