Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase genes

A cross-sectional study was performed to evaluate the influence of polymorp hisms in the delta -aminolevulinic acid dehydratase (ALAD) and vitamin D re ceptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid ( DMSA)-chelatable lead levels in 798 lead workers and 135 controls without o ccupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by Cd-109-induced K-shell X-ray fluorescence, an d DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after o ral administration of 10 mg/kg DMSA. The primary goals of the analysis were to examine blood lead, tibia lead, and DMSA-chelatable lead levels by ALAD and VDR genotypes, controlling for covariates; and to evaluate whether ALA D and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 mug/dL), tibia lead ((-)7-338 mu g Pb/g bone mineral), and DMSA-chelatable lead (4.8-2,103 mug) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele and there were no homozygotes. For VDR, 10.7% (n = 85) had t he Bb genotype, and 0.5% (n = 4) had the BB genotype. Although the ALAD and VDR genes are located on different chromosomes, lead workers homozygous fo r the ALAD(1) allele were much less likely to have the VDR bb genotype (cru de odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjust ed analyses, subjects with the ALAD(2) allele had higher blood lead levels (on average, 2.9 mug/dL, p = 0.07) but no difference in tibia lead levels c ompared with subjects without the allele. In adjusted analyses, lead worker s with the VDR B allele had significantly (p < 0.05) higher blood lead leve ls (on average, 4.2 <mu>g/dL), chelatable lead levels (on average, 37.3 mug ), and tibia lead levels (on average, 6.4 mug/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD g ene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well.