The relationship between occupational lead exposure and PON1 genotypes and lipid profiles

[[abstract]]Background:Once absorbed into the body, lead becomes widely distributed and interacts with a number of enzyme systems. In some epidemiological studies, lead exposure may result in hurt of cardiovascular function in humans. On the other hand, paraoxonase-1 (PON1) is an HDL-associated serum enzyme, previously known for detoxification of organophosphorus insecticides. Evidence has shown that PON1 protects low-density lipoproteins (LDL) from oxidative damage both in vitro and in vivo. The aim of this study is to investigate whether occupational lead exposure is associated with lipid profiles with disturbing paraoxonase, and how PON1 polymorphisms may modify the association.Methods:Five hundred ninety-seven workers were recruited from lead manufacturing factories. Three PON1 polymorphisms (Q192R, L55M, -108C/T) were determined by PCR-RFLP method. PON1 activities were analysed using SpectraMax. Blood lead, lipid profiles and serum biochemical data were gathered from health examination. The questionnaire comprised personnel characters, smoking and drinks.Results:PON1 R192 alloenzyme has more hydrolytic activity toward paraoxon, Q192 alloenzyme has more hydrolytic activities toward phenol acetate and diazoxon. In multiple linear regressions, after controlling potential confounders, blood lead levels were associated with decreased log TG and T-CHO. Blood lead levels were negativity correlated with serum PON1 activity for hydrolyzing phenyl acetate and paraoxon respectively. The correlation between blood lead levels and serum PON1 activity was affected by the PON1 192 genotype. The effects were more obvious for subjects who carry the R allele.Conclusion:The main finding of this study was that the significant negative correlation between blood lead and PON1 activities. Although the mechanism was not clear, the association between blood lead and low PON1 activities was biologically plausible and could be due to either increased synthesis or decreased removal of lipid profiles. PON1 has been implicated in the pathogenesis of cardiovascular disease, so we can follow-up this cohort, and observe the risk of developing cardiovascular disease