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Associations of Blood Lead, Dimercaptosuccinic Acid-Chelatable Lead, and Tibia Lead with Polymorphisms in the Vitamin D Receptor and -Aminolevulinic Acid Dehydratase Genes

Brian S. Schwartz,^1,2,3 Byung-Kook Lee,⁴ Gap-Soo Lee,⁴ Walter F. Stewart,^1,3 David Simon,³ Karl Kelsey,⁵ and Andrew C. Todd⁶

¹Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland, USA
²Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
³Department of Epidemiology, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland, USA
⁴Institute of Industrial Medicine, Soonchunhyang University, Chonan, Korea
⁵Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts, USA
⁶Department of Community and Preventive Medicine, Mount Sinai Medical Center, New York, New York, USA.

Abstract

A cross-sectional study was performed to evaluate the influence of polymorphisms in the -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. Key words: -aminolevulinic acid dehydratase, bone lead, cross-sectional study, lead, polymorphisms, vitamin D receptor, X-ray fluorescence. Environ Health Perspect 108:949-954 (2000) . [Online 31 August 2000]

http://ehpnet1.niehs.nih.gov/docs/2000/108p949-954schwartz/ abstract.html

Address correspondence to B.S. Schwartz, Division of Occupational and Environmental Health, Johns Hopkins School of Hygiene and Public Health, Room 7041, 615 Wolfe Street, Baltimore, MD 21205 USA. Telephone: (410) 955-4158. Fax: (410) 955-1811. E-mail: bschwart@jhsph.edu

We thank P.J. Parsons for performing the urine lead measurements and Y-B. Kim, K-Y. Hwang, S-S. Lee, and K-D. Ahn for assisting in data collection in Korea.

This research was supported by grant ES07198 (to B.S.S.) from the National Institute of Environmental Health Sciences.

Received 17 April 2000 ; accepted 30 May 2000.