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Bruce H. Alexander,¹ Harvey Checkoway,^1,2 Paola Costa-Mallen,¹ Elaine M. Faustman,^1,2,3,4 James S. Woods,^1,2 Karl T. Kelsey,⁵ Chris van Netten,⁶ and Lucio G. Costa²

¹Department of Environmental Health, ²NIEHS Center for Ecogenetics and Environmental Health, ³Institute for Risk Analysis and Risk Communication, and ⁴Center on Human Development and Disability, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195 USA
⁵Occupational Health Program, Department of Environmental Health and Department of Cancer Biology, Harvard School of Public Health, Boston, MA 02115 USA
⁶Department of Health Care and Epidemiology, University of British Columbia, Vancouver, BC V6T 123 Canada

Abstract

The gene that encodes -aminolevulinic acid dehydratase (ALAD) has a polymorphism that may modify lead toxicokinetics and ultimately influence individual susceptibility to lead poisoning. To evaluate the effect of the ALAD polymorphism on lead-mediated outcomes, a cross-sectional study of male employees from a lead-zinc smelter compared associations between blood lead concentration and markers of heme synthesis and semen quality with respect to ALAD genotype. Male employees were recruited via postal questionnaire to donate blood and urine for analysis of blood lead, zinc protoporphyrin (ZPP) , urinary coproporphyrin (CPU) , and ALAD genotype, and semen samples for semen analysis. Of the 134 workers who had ALAD genotypes completed, 114 (85%) were ALAD1-1 (ALAD1) and 20 (15%) were ALAD1-2 (ALAD2) . The mean blood lead concentrations for ALAD1 and ALAD2 were 23.1 and 28.4 µg/dl (p = 0.08) , respectively. ZPP/heme ratios were higher in ALAD1 workers (68.6 vs. 57.8 µmol/mol ; p = 0.14) , and the slope of the blood lead ZPP linear relationship was greater for ALAD1 (2.83 vs. 1.50, p = 0.06) . No linear relationship between CPU and blood lead concentration was observed for either ALAD1 or ALAD2. The associations of blood lead concentration with ZPP, CPU, sperm count, and sperm concentration were more evident in workers with the ALAD1 genotype and blood lead concentrations =40 µg/dl. The ALAD genetic polymorphism appears to modify the association between blood lead concentration and ZPP. However, consistent modification of effects were not found for CPU, sperm count, or sperm concentration. Key words: -aminolevulinic acid dehydratase, coproporphyrin, genotype, lead, semen, smelters, zinc protoporphyrin. Environ Health Perspect 106:213-216 (1998) . [Online 12 March 1998]

http://ehpnet1.niehs.nih.gov/docs/1998/106p213-216alexander/ abstract.html

Address correspondence to B.H. Alexander, Department of Environmental Health, Box 358772, University of Washington, Seattle, WA 98195 USA.

This research was sponsored by National Institutes of Environmental Health Sciences grants ES04696 and ES07033, National Institutes of Health grants ES005947 and ES00002, National Institute for Occupational Safety and Health grant R03-OH02966, and Department of Energy grant DE-FC01-95EW. Bruce H. Alexander and Paola Costa-Mallen were supported by NIEHS training grant T32-ES07262.

Received 14 July 1997 ; accepted 17 November 1997.