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C. Mark Smith,^1,2,3 Xi Wang,² Howard Hu,^2,4 and Karl T. Kelsey^1,2

¹Department of Cancer Biology and ²Occupational Health Program, Harvard School of Public Health, Boston, MA 02115 USA
³Massachusetts Department of Environmental Protection, Boston, MA 02108 USA
⁴Department of Medicine, Channing Laboratory, Brigham and Womens Hospital, Harvard Medical School, Boston, MA 02115 USA

Abstract

Associations between the presence of a constitutional variant of -aminolevulinic acid dehydratase (ALAD-2) and lead concentrations in blood and bone, as well as between this allele and indices of kidney function, were investigated among 691 members of a construction trade union. The average blood lead level in this group was 7.78 µg/dl. No significant difference was observed in blood lead concentration in ALAD-2 carriers compared to those homozygous for the more common ALAD-1 allele (7.78 (± 3.62 µg Pb/dl vs. 7.73 (± 3.48 µg Pb/dl, respectively ; p = 0.73) . Bone lead was measured in a subset of 122 of the study subjects. Patella minus tibia lead concentrations for each individual averaged 3.35 ± 11.99 µg Pb/g bone mineral in ALAD-1 homozygotes and 8.62 ± 9.47 µg Pb/g bone mineral in ALAD-2 carriers (p = 0.06) . Comparisons of blood urea nitrogen (BUN) and uric acid by genotype indicated elevated levels among ALAD-2 individuals (p = 0.03 and 0.07, respectively) . In logistic regression models accounting for other variables potentially associated with BUN and uric acid levels, BUN was significantly associated with blood lead levels (p = 0.01) . Associations of BUN and uric acid levels with ALAD-2 were of borderline statistical significance in these models (p = 0.06 and 0.07) . Taken together, these results suggest that the ALAD-2 genotype may influence the pharmacokinetic distribution and chronic renal toxicity of lead, perhaps due to differential binding of lead to the variant protein. Key words: aminolevulinic acid dehydratase, biomarkers, bone lead, kidney function, lead, susceptibility. Environ Health Perspect 103:248-253 (1995)

Address correspondence to K.T. Kelsey, Department of Cancer Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115 USA.

This work was supported in part by NIEHS ES-00002, NIOSH, the United Brotherhood of Carpenters Health and Safety Fund, NIEHS ES 05257-01A1 and P 42-ES05947. The K-XFR instrument used in this study was developed by ABIOMED, Inc. (Danvers, Massachusetts) , with support from NIH (SBIR 2 R44 ES03918-020) . Special thanks to Lucille Pothier for her assistance in the statistical analyses and John Bollinger for manuscript preparation. We also thank John Wetmur for providing us with the ALAD sequences and the members of the United Brotherhood of Carpenters and Joiners of America for their participation and interest and the Carpenters Health and Safety Fund of North America, in particular Edward J. Gorman, III, for organizing the medical screening.

Received 21 September 1994 ; accepted 13 December 1994.