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

Manal Kamal1, Mona M. Fathy1, Mohamed Elkhatib1, Manal Hasan2, and Sherein S. Ghaleb3

1 Clinical and Chemical Pathology, Internal Medicine,
2 Industrial Medicine and Occupational Diseases, and
3 Forensic Medicine, Faculty of Medicine, Cairo University, Egypt

Corresponding author: Dr. Manal Kamal
    Clinical and Chemical Pathology, Internal Medicine
    4 Abd El Hadi street,
    El Manial, Cairo, Egypt
    E-mail: manalmk@ yahoo.com

CEJOEM 2007, Vol.13. No.3-4.: 267-298


Key words:
atherosclerosis, lead, LDL, paraoxonase and polymorphism


Abstract:
Background: The continued occurrence of occupational lead overexposure 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. An association was found between lead exposure and serum cholesterol and lipoprotein levels in workers of battery and recycling factories. Previous studies have shown that lead and several other metal ions are able to inhibit PON1 activity in vitro thus producing atherosclerosis.
    Objectives: The aim of the present study was to find out whether lead exposure has any effects on serum PON1 activity and lipid profile levels. Also, to understand the possible interaction between lead and polymorphism of the gene that encodes protein known to be involved in the regulation of atherosclerosis.
    Subjects and methods: This study was carried out on 90 males working in a lead-acid battery manufactory. Full medical history was taken; physical examination and blood pressure measurements were performed. Blood lead levels, lipid profile, liver and renal function tests in addition to blood glucose were done to all workers. Buffy coat isolated from EDTA-treated blood was used for genomic DNA preparation for genotyping, whereas serum was collected for the PON1 activity assay. The workers were divided according to their blood lead level into three groups: group 1 (lead less than 40 µg/dl), group 2 (lead: 40-60 µg/dl) and group 3 with lead level >60 µg/dl).
    Results: No difference was found in systolic and diastolic blood pressure in different groups. Only total cholesterol and LDL-c levels were significantly different among the three groups, with the highest-exposure group having the highest level of total cholesterol and LDL-C. Moreover, the PON1 activity of the high-exposure group was lower than the low-exposure group, however, this difference didn't reach statistical significance. Blood lead was positively correlated with total cholesterol and LDL-c (r=0.2, P=0.04). A highly significant negative correlation was found between paraoxonase activity and the duration of exposure to lead (r=-0.3, P=0.005). Blood lead was found to be an independent factor affecting serum PON1 activity as a significant negative correlation was found between paraoxonase and blood lead in all groups (r=-0.2, P=0.05). No relation was found between PON1 genotype and blood lead level.
    Conclusion: Occupational lead exposure is associated with decreased serum PON1 activity which was more profound with increasing duration of exposure to lead. Because of the protective role of PON1 in the development of atherosclerosis, decrease in serum PON1 activity could be a risk factor among lead exposed workers.


Received: 27 May 2008
Accepted: 17 July 2008

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