Impact of Lead Exposure on Serum Paraoxonase 1 (PON1) Activity and Genotype in Occupationally-Exposed Egyptian Workers

The continued occurrence of occupational lead over-exposure and lead poisoning in Egypt remains a serious problem despite awareness of its adverse health effects. Lead exposure causes cardiac and vascular damage in experimental animals. Most studies of the cardiovascular effects of lead in humans have focused on lead's causal relationship with hypertension. Meanwhile, an association between lead exposure and serum cholesterol and lipoprotein levels was found in workers of battery and recycling factories. A hypothesis was originally based on the finding that purified paraoxonase 1 (PON1) was highly effective in preventing lipid peroxidation of LDL. Lead and several other metal ions were claimed to inhibit PON1 activity in vitro thus producing atherosclerosis. PON1 has 2 amino acid polymorphisms; a meta-analysis study reveals a statistically significant overall association between the PON1 192 R allele and the presence of coronary heart disease.

The aim of the present study was to study whether lead exposure has any effects on serum PON1 activity and lipid profile levels in addition to, understand the possible interaction between lead and polymorphisms of genes that encode proteins known to be involved in regulation of atherosclerosis.

This study was carried out on 90 workers (90 males) in a lead-acid battery manufactory. Full medical history and clinical examination were performed with special emphasis on blood pressure measurement. Blood samples were withdrawn from every selected worker for estimation of blood lead levels, the separated serum was used for estimating lipid profile as well as and liver and renal function tests in addition to blood glucose levels and PON1 activity assay. Buffy coat isolated from EDTA-treated blood was used for genomic DNA preparation for genotyping. According to the obtained blood lead level, subjects are classified into 3 groups: Group I with blood lead level <40μg/dl, group II with a level ranged between 40 and 60 μg/dl and group III with a level above 60 μg/dl.

No statistically significant difference was found in systolic and diastolic blood pressure between the different groups. Only total cholesterol and LDL-C levels were statistically significantly different among the three groups, with the highest levels in the highest-exposure group. Moreover, the average paraoxonase activity of the highexposure group was lower than the low-exposure group however, it didn't reach statistical significance. Simple linear correlation analysis revealed that, blood lead was positively correlated with total cholesterol and LDL C (P=0.04). In addition, a highly significant negative correlation was found between paraoxonase and both age of the workers and their duration of exposure (P=0.002, 0.005, respectively). A significant negative correlation was found between paraoxonase and blood lead in all groups studied as one. Blood lead was found to be an independent factor affecting serum PON1 activity P=0.05. The present study failed to find that the subjects who are homozygous for the R allele are more susceptible to lead toxicity than are subjects of other genotypes.

Increasing the duration of occupational lead exposure is associated with decreased serum PON1 activity, which has a protective role against the development of atherosclerosis, predisposing these workers to premature atherosclerosis. Serum PON1 activity could be used as a bio-marker to monitor the cardiovascular health among lead workers.