TY - JOUR
T1 - Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and δ-aminolevulinic acid dehydratase genes
AU - Schwartz, Brian S.
AU - Lee, Byung Kook
AU - Lee, Gap Soo
AU - Stewart, Walter F.
AU - Simon, David
AU - Kelsey, Karl
AU - Todd, Andrew C.
PY - 2000
Y1 - 2000
N2 - A cross-sectional study was performed to evaluate the influence of polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by 109Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after oral 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 ALAD and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 μg/dL), tibia lead (-7-338 μg Pb/g bone mineral), and DMSA-chelatable lead (4.8-2, 103 μg) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD2 allele and there were no homozygotes. For VDR, 10.7% (n = 85) had the 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 for the ALAD1 allele were much less likely to have the VDR bb genotype (crude odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjusted analyses, subjects with the ALAD2 allele had higher blood lead levels (on average, 2.9 μg/dL, p = 0.07) but no difference in tibia lead levels compared with subjects without the allele. In adjusted analyses, lead workers with the VDR B allele had significantly (p<0.05) higher blood lead levels (on average, 4.2 μg/dL), chelatable lead levels (on average, 37.3 μg), and tibia lead levels (on average, 6.4 μg/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD gene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well.
AB - A cross-sectional study was performed to evaluate the influence of polymorphisms in the δ-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by 109Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after oral 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 ALAD and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 μg/dL), tibia lead (-7-338 μg Pb/g bone mineral), and DMSA-chelatable lead (4.8-2, 103 μg) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD2 allele and there were no homozygotes. For VDR, 10.7% (n = 85) had the 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 for the ALAD1 allele were much less likely to have the VDR bb genotype (crude odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjusted analyses, subjects with the ALAD2 allele had higher blood lead levels (on average, 2.9 μg/dL, p = 0.07) but no difference in tibia lead levels compared with subjects without the allele. In adjusted analyses, lead workers with the VDR B allele had significantly (p<0.05) higher blood lead levels (on average, 4.2 μg/dL), chelatable lead levels (on average, 37.3 μg), and tibia lead levels (on average, 6.4 μg/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD gene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well.
KW - Bone lead
KW - Cross-sectional study
KW - Lead
KW - Polymorphisms
KW - Vitamin D receptor
KW - X-ray fluorescence
KW - δ-Aminolevulinic acid dehydratase
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U2 - 10.1289/ehp.00108949
DO - 10.1289/ehp.00108949
M3 - Article
C2 - 11049814
AN - SCOPUS:0033677264
SN - 0091-6765
VL - 108
SP - 949
EP - 954
JO - Environmental health perspectives
JF - Environmental health perspectives
IS - 10
ER -