Lead exposure is associated with decreased serum paraoxonase 1 (PON1) activity and genotypes
Lead exposure is associated with decreased serum paraoxonase 1 (PON1) activity and genotypes
复制标题
DOI：
10.1289/ehp.9163
复制
发表时间：
2006-08-01
影响因子：
10.4
通讯作者：
Chuang, Hung-Yi
中科院分区：
文献类型：
--
作者：
Li, Wan-Fen;Pan, Mei-Hung;Chuang, Hung-Yi
铅暴露导致实验动物的心脏和血管损伤。然而，关于铅暴露与人类心血管功能障碍之间的因果关系存在相当大的争议。对氧磷酶1（PON 1）是一种高密度脂蛋白相关的抗氧化酶，能够水解氧化脂质，从而防止动脉粥样硬化。以往的研究表明，铅和其他几种金属离子能够抑制PON 1活性在体外。为了研究铅暴露是否对血清PON 1活性产生影响，我们对铅电池制造厂和铅回收厂的工人进行了横断面研究。分析血液样本的全血铅水平、血清PON 1活性和三种常见的PON 1多态性（Q192 R、L55 M、-108C/T）。该队列的平均血铅水平（+/- SD）为27.1 +/- 15 μ g/dL。多元线性回归分析显示，铅作业工人血铅水平与血清PON 1活性降低显著相关（p < 0.001）。这种负相关性在携带R192等位基因的工人中更为明显，该等位基因被认为是冠心病的危险因素。综上所述，我们的研究结果表明，由于铅暴露导致的血清PON 1活性降低可能使个体更容易患动脉粥样硬化，特别是R192等位基因纯合子的受试者。
Lead exposure causes cardiac and vascular damage in experimental animals. However, there is considerable debate regarding the causal relationship between lead exposure and cardiovascular dysfunction in humans. Paraoxonase 1 (PON1), a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus protects against atherosclerosis. Previous studies have shown that lead and several other metal ions are able to inhibit PON1 activity in vitro. To investigate whether lead exposure has influence on serum PON1 activity, we conducted a cross-sectional study of workers from a lead battery manufactory and lead recycling plant. Blood samples were analyzed for whole-blood lead levels, serum PON1 activity, and three common PON1 polymorphisms (Q192R, L55M, -108C/T). The mean blood lead level (+/- SD) of this cohort was 27.1 +/- 15 mu g/dL. Multiple linear regression analysis showed that blood lead levels were significantly associated with decreased serum PON1 activity (p < 0.001) in lead workers. This negative correlation was more evident for workers who carry the R192 allele, which has been suggested to be a risk factor for coronary heart disease. Taken together, our results suggest that the decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis, particularly subjects who are homozygous for the R192 allele.