Lead Exposure Is Associated with Decreased Serum Paraoxonase 1 (PON1) Activityand Genotypes

Abstract

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 μg/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.

Electrocardiogram (ECG) Abnormality Among Residents in Arseniasis-Endemic and Non-Endemic Areas of Southwestern Taiwan – A Study of Gene-Gene and Gene-Environment Interactions

“…PON1 directly form part of HDL particles whereas PON2 found in endothelial cells, smooth muscle cells and macrophages that possesses antioxidant properties similar to PON1 by delays cellular oxidative stress and prevents apoptosis in vascular endothelial cells 70,71 . Regarding three common polymorphisms in coding region of the human PON1 gene, the frequencies of Q192R, L55M, and C-108T for Taiwanese population were similar to those reported in the literature for the Chinese population 72,73 . Besides, we confirmed that paraoxonase, diazoxonase and arylesterase activities were directly influenced by the Q192R and C-108T polymorphisms.…”

Copper Deficiency, Lead, and Paraoxonase: Li et al. Respond

“…Klevay suggested that the decrease of PON1 activity in lead workers, as we reported in our article (Li et al 2006), might be due to copper deficiency induced by lead intoxication. Because the scope of our study did not include the interaction between lead and copper, we did not measure plasma copper level, ceruloplasmin, or superoxide dismutase (SOD) activity in our cohort.…”

Metal pollutants and cardiovascular disease: Mechanisms and consequences of exposure

“…For example, the cardioprotective antioxidant activity of HDL is partially mediated by paraoxonase activity, an enzyme that is closely bound to the HDL particle and involved in inhibition of LDL oxidation. Lead, as well as other metals, can inactivate paraoxonase and, therefore, promote LDL oxidation and atherosclerosis development 22,23, 24 .…”