| Summary: | 碩士 === 高雄醫學大學 === 公共衛生學研究所碩士班 === 92 === Background:
Once absorbed into the body, lead becomes widely distributed and interacts with a number of enzyme systems. Lead poisoning cause cardiac and vascular damage in experimental animals. In epidemiology, lead exposure has been related to cardiovascular dysfunctions in humans. Paraoxonase-1（PON1）is an HDL-associated serum enzyme, previously known for its ability to detoxify 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 and how PON1 may modify the association.
Methods:
474 and 124 workers were recruited from two lead manufacturing factories, separately. Three common PON1 polymorphisms（Q192R, L55M, -108C/T）were determined by PCR-RFLP method. Serum PON1 activities were measured using a microfiter plate reader （SpectraMax, Molecular Devices）. Blood samples were analyzed for lipid profiles（TG, TC, HDL）and blood lead levels. Information of personal characteristics, smoking and drinking habits were obtained by using of a questionnaire.
Results：
（1）PON1 R192 alloenzyme has higher hydrolytic activity toward paraoxon, Q192 alloenzyme has higher hydrolytic activities toward phenol acetate and diazoxon.
（2） In multiple linear regression, after controlling potential confounders, blood lead levels were associated with decreased log TG and T-CHO.
（3）Blood lead levels were negativity correlated with serum PON1 activity for hydrolyzing phenyl acetate and paraoxon respectively.
（4）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:
In epidemiology, only a few studies have been conducted to examine the relationship between blood lead levels and lipid profiles. This study showed a weak and negative correlation between blood lead levels, log TG and TC levels, which is inconsistent with previous reports. The main finding of this study was the negative correlation between blood lead levels and PON1 activities. Although the mechanism was not clear, the association between blood lead levels and low PON1 activities was biologically plausible and could be due to direct interaction between lead, ion and PON1 structure. PON1 has been implicated in the pathogenesis of cardiovascular disease, so we will follow-up this cohort and observe its risk for developing clinical cardiovascular symptoms. Therefore, we can further examine whether the inhibitory effects of lead exposure on PON1 result in real damage of the cardiovascular system.
Key words: Lead, Paraoxonase-1 (PON1), Lipid profiles.
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