Abstract
Background: Lead inhibits the enzymes in heme biosynthesis, mainly reducing δ-aminolevulinic acid dehydratase (ALAD) activity, which could be an available biomarker. The aim of this study was to detect the threshold of δ-aminolevulinic acid dehydratase activity reduced by lead exposure. Methods: We collected data on 121 lead workers and 117 non-exposed workers when annual health examinations were performed. ALAD activity was determined by the standardized method of the European Community. ALAD G177C (rs1800435) genotyping was conducted using the polymerase chain reaction and restricted fragment length polymorphism (PCR-RFLP) method. In order to find a threshold effect, we used generalized additive models (GAMs) and scatter plots with smoothing curves, in addition to multiple regression methods. Results: There were 229 ALAD1-1 homozygotes and 9 ALAD1-2 heterozygotes identified, and no ALAD2-2 homozygotes. Lead workers had significantly lower ALAD activity than non-exposed workers (41.6 ± 22.1 vs. 63.3 ± 14.0 U/L, p < 0.001). The results of multiple regressions showed that the blood lead level (BLL) was an important factor inversely associated with ALAD activity. The possible threshold of BLL affecting ALAD activity was around 5 μg/dL. Conclusions: ALAD activity was inhibited by blood lead at a possible threshold of 5 μg/dL, which suggests that ALAD activity could be used as an indicator for lead exposure regulation.
Highlights
Leaded gasoline was phased out in Taiwan in 2000, lead continues to be a public health concern due to its industrial uses
The goal of this study was to detect the threshold of δ-aminolevulinic acid dehydratase activity reduced by lead exposure and determine if ALAD activity was modified by ALAD genotypes
We found that when the concentration of blood lead in group 3 reached the range of 10.01 to 15.0 μg/dL, ALAD enzyme activity began to be significantly lower than group 1
Summary
Leaded gasoline was phased out in Taiwan in 2000, lead continues to be a public health concern due to its industrial uses. Lead inhibits three enzymes in the heme biosynthesis pathway, δ-aminolevulinic acid dehydratase (ALAD), coporphyrinogen oxidase, and ferrochelatase, and its effects on ALAD are the most profound. ALAD inhibition results in a buildup of aminolevulinic acid detectable in the plasma and urine. Lead inhibits the enzymes in heme biosynthesis, mainly reducing δ-aminolevulinic acid dehydratase (ALAD) activity, which could be an available biomarker. The aim of this study was to detect the threshold of δ-aminolevulinic acid dehydratase activity reduced by lead exposure. Methods: We collected data on 121 lead workers and 117 non-exposed workers when annual health examinations were performed. Lead workers had significantly lower ALAD activity than non-exposed workers (41.6 ± 22.1 vs 63.3 ± 14.0 U/L, p < 0.001). The results of multiple regressions showed that the blood lead level (BLL) was an important factor inversely associated with ALAD activity.
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