Associations of delta-aminolevulinic acid dehydratase genotype with plant, exposure duration, and blood lead and zinc protoporphyrin levels in Korean lead workers

Abstract

Previous studies have suggested that polymorphisms in delta-aminolevulinic acid dehydratase (ALAD), a heme synthetic enzyme, may be associated with differences in blood lead levels, perhaps due to differential binding of lead in erythrocytes. The authors examined associations of ALAD genotype with blood lead and zinc protoporphyrin (ZPP) levels, exposure duration, sex, and plant in 308 currently exposed lead workers in three lead storage battery manufacturing plants in the Republic of Korea in 1993. The overall prevalence of the variant allele, ALAD2, was 11%, but prevalence varied by plant (p = 0.02: 8.6% in plant A, 20% in plant B, and 22% in plant C). While ALAD2 was not associated with mean blood lead levels, the allele was associated with blood lead levels greater than or equal to 40 micrograms/dl (crude odds ratio (OR) = 2.6, 95% confidence interval (CI) 1.1-6.3; adjusted OR = 2.3, 95% CI 0.8-6.2, with adjustment for sex, plant, and exposure duration) and with exposure durations greater than 6 years (adjusted OR = 2.5, 95% CI 1.2-5.4, with adjustment for blood lead, sex, and plant). Among workers in plant C, the highest exposure plant, ALAD2 was associated with lower ZPP levels when controlling for blood lead levels. These data suggest that lead toxicokinetics may be modified by ALAD genotype and that ALAD2 may be protective for the health effects of lead. ALAD genotype also appears to have been a selection factor for current lead exposure status in the studied workers.