δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers’ peripheral nervous system

There is a wide variation in sensitivity to lead (Pb) exposure, which may be due to genetic susceptibility towards Pb. We investigated whether a polymorphism (rs1800435) in the δ-aminolevulinic acid dehydratase (ALAD) gene affected the toxicokinetics and toxicodynamics of Pb. Among 461 Chinese Pb-exposed storage battery and 175 unexposed workers, allele frequencies for the ALAD1 and ALAD2 alleles were 0.968 and 0.032, respectively. The Pb-exposed workers had a higher fraction of the ALAD1-2/2-2 genotype than unexposed workers (7.8% vs. 2.3%, p = 0.01). The Pb levels in blood (B-Pb) and urine (U-Pb) were higher in Pb-exposed workers carrying the ALAD2 allele compared to homozygotes for ALAD1 (median B-Pb: 606 vs. 499 μg/L; U-Pb: 233 vs. 164 μg/g creatinine), while there was no statistically significant difference in the unexposed controls (median: 24 vs. 37 μg/L, and 3.9 vs. 6.4 μg/g creatinine, respectively). High B-Pb and U-Pb were associated with statistically significantly lower sensory and motor conduction velocities in the median, ulnar and peroneal nerves. At the same B-Pb and U-Pb, ALAD1 homozygotes had lower conduction velocities than the ALAD2 carriers. There were similar trends for toxic effects on haem synthesis (zinc protoporphyrin and haemoglobin in blood) and renal function (albumin and N-acetyl-d-β-acetylglucosaminidase in urine), but without statistical significance. There was no difference in Pb toxicokinetics and toxicodynamics associated with VDR BsmI polymorphism. Our results show that the ALAD genotype modifies the relationship between Pb and its toxic effects on the peripheral nervous system. This must be considered in the assessment of risks at Pb exposure.

► Variation in sensitivity to Pb exposure may be due to genetic susceptibility. ► We investigated whether ALAD genotype affected Pb toxicity among Chinese workers. ► Higher Pb was associated with lower conduction velocities in peripheral nerves. ► Associations between Pb and its neurological effects were modified by ALAD genotype.