| Objective: Exposure to lead can result in significant adverse health effects to multiple organ systems. Lead toxicity is still an issue of public health concern. With the similar levels of lead exposure, some individuals are vulnerable to lead toxic effects, which indicate there is lead toxicity susceptibility among individuals. δ-Aminolevulinic acid dehydratase (ALAD) enzyme (EC4.2.1.24) is the second enzyme in the heme biosynthetic pathway, which is well inhibited by lead. It is known to polymorphisms in the population, with two common alleles, ALAD-1 and ALAD-2. These two alleles determine three isozymes, designated 1-1, 1-2 and 2-2. The different charges of three isozmes can affect lead pharmacokinetics, so the researches of ALAD gene polymorphisms contribute to study lead genetic susceptibility further. The aim of our work was to understand the role of ALAD gene polymorphisms to lead genetic susceptibility, provide scientific proof for finding the sensitive factors of lead toxicity, prove into whether there were differences in the mechanism, clinic symptoms and therapy reaction of lead toxicity among ALAD genotypes or not, and thus to contribute to further protect the health of lead toxicity susceptibility groups.Method: The interviewees were selected from the Han workers those were exposed to lead and accepted physical examinations in Huaxi Fourth University Hospital during Apr. to Oct., 2003. Their age was from 22 years old to 59 years old and length of work was from 1 year to 42 years. 156 workers (51 men and 105 women) were accepted into the study if they had no history of diseases, such as heart disease, hypertension, diabetes mellitus, cancer and gout. Questionnaire was adopted to investigate demographic information and syndromes of lead workers, and physical examinations were conducted to check health status. 156 blood samples and 148 urine samples were collected, analyzing lead exposure biomarkers (lead level in blood and urine, ALA and ZPP), effect biomarkers (BUN, serum creatinine, urine creatinine, NAG) and necessary elements (Ca, Fe and Zn). ALAD polymorphisms were determined by PCR-RLFP. The relationship between ALAD polymorphisms and lead toxicity was studied by genotypes.Results: (T)Of the lead exposed workers analyzed for ALAD genotypes, 146 (93.6%) were ALAD1-1 and 10 (6.4%) were ALAD 1-2. No workers were homozygous for the ALAD-2 allele. The frequency of ALAD-1 and ALAD-2 were 0.9679 and 0.0321, respectively. ?Workers health status by genotypes: The main syndromes included dreams, insomnia and dizziness. Workers with ALAD 1-1 genotype had higher the incident rate of syndromes than those with the ALAD 1-2 genotype, however the difference was no significant (P>0.05). There were no significant differences in blood pressure, pulse, body mass index (BMI) and liver function between ALAD 1-1 genotype and ALAD 1-2 genotype. The blood lead levels and PLT in ALAD1-1 genotype were significantly higher than that in ALAD 1-2 genotype (PO.05). Grouped by work age, the blood lead levels in ALAD1-1 genotype were higher than that in ALAD 1-2 genotype when length of work was less than 5 years. ?Study the effect of ALAD gene polymorphisms to lead toxicity: The blood lead and urine lead levels in ALAD1-1 genotype were higher than that in ALAD 1-2 genotype, 1.31umol/l vs. 0.86umol/l (P<0.05), 59.49umol/l vs.22.30umol/l(P — 0.06), respectively. The correlations between blood lead and serum calcium, iron or zinc were negative, and the serum iron or zinc in ALAD1 -2 genotype were significantly higher than that in ALAD1-1 genotype, and similar findings were also observed in the work type of storage battery. However, in the work type of cable the serum zinc in ALAD 1-2 genotype was significantly lower than that in ALAD1-1 genotype, whereas serum calcium was significantly higher than that in ALAD1-1 genotype (P<0.05). ALA and ZPP in ALAD1-1 genotype were significantly higher than that in ALAD 1-2, and the correlation between blood lead levels and ALA or ZPP was positive. Serum iron levels can inhibit the synthesization of ZPP. But there was no difference in the correlation between ALAD genotypes and ALA or ZPP in the multi-linear regression. There were no significant differences on BUN, urine creatinine, NAG, or creatinine clearance by ALAD genotypes. However, serum creatinine in ALAD1-1 genotype was higher than that in ALAD 1-2 genotype, and the multi-linear regression indicated the negative correlation between serum creatinine and blood lead levels and the positive correlation between serum creatinine and BMI (PO.05). Using the multi-linear regression to analyze data, it showed that work type, gender and serum zinc were influential factors of blood lead level, but no significant difference was found between ALAD genotypes and blood lead levels.Conclusion: (T)In the Hans lead exposure workers, the gene frequencies of the ALAD-1 and ALAD-2 alleles were 0.9679 and 0.0321, respectively. This finding was similar with the Hans population in that gene frequencies were reported early. (2) ALAD gene polymorphisms could modify lead pharmacokinetics, ALAD 1-1 individuals might be an increased risk compared to ALAD-2 carriers to disturbance in heme biosynthetic pathway and ALAD-2 might serve some protective role in lead-induced neurotixixcity. ?The correlation between serum calcium, iron or zinc and blood lead was negative. Subjects with ALAD 1-2 genotype were less sensitive to lead toxicity than those with ALAD1-1 genotype. ?The health status of lead exposure workersshowed that there were no different clinic symptoms among various ALAD genotypes. However, some biomarkers of lead toxicity show different between ALAD genotypes indicated there might be different in the early response of lead toxicity by ALAD genotypes. ?The research indicated that rose lead levels had a little influence on renal function and hemopoietic function, but no differences were found in liver function, renal function, hemopoietic function and blood pressure by genotypes. ?The research results also indicated that there might be differences in lead toxicity mechanism, clinic symptoms and therapy reaction by genotypes, so study further is necessary to identify the risk of lead toxicity and provide science ways to prevent worker health.
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