Lead and δ-Aminolevulinic Acid Dehydratase Polymorphism: Where Does It Lead? A Meta-Analysis

BACKGROUND: Lead poisoning affects many organs in the body. Lead inhibits δ-aminolevulinic acid dehydratase (ALAD), an enzyme with two co-dominantly expressed alleles, ALAD1 and ALAD2. OBJECTIVE: Our meta-analysis studied the effects of the ALAD polymorphism on a) blood and bone lead levels and b) indicators of target organ toxicity. DATA SOURCE: We included studies reporting one or more of the following by individuals with genotypes ALAD1-1 and ALAD1-2/2-2: blood lead level (BLL), tibia or trabecular lead level, zinc protoporphyrin (ZPP), hemoglobin, serum creatinine, blood urea nitrogen (BUN), dimercaptosuccinic acid–chelatable lead, or blood pressure. DATA EXTRACTION: Sample sizes, means, and standard deviations were extracted for the genotype groups. DATA SYNTHESIS: There was a statistically significant association between ALAD2 carriers and higher BLL in lead-exposed workers (weighted mean differences of 1.93 μg/dL). There was no association with ALAD carrier status among environmentally exposed adults with BLLs < 10 μg/dL. ALAD2 carriers were potentially protected against adverse hemapoietic effects (ZPP and hemoglobin levels), perhaps because of decreased lead bioavailability to heme pathway enzymes. CONCLUSION: Carriers of the ALAD2 allele had higher BLLs than those who were ALAD1 homozygous and higher hemoglobin and lower ZPP, and the latter seems to be inversely related to BLL. Effects on other organs were not well delineated, partly because of the small number of subjects studied and potential modifications caused by other proteins in target tissues or by other polymorphic genes

PANEL DISCUSSION: Lead and Copper in Drinking Water

Proceedings of the 1993 Georgia Water Resources Conference, April 20-21, 1993, Athens, Georgia.Panel Discussions: Population Exposure to Lead and Copper, Henry Abadin, Agency for Toxic Substances and Disease Registry, 1600 Cliffton Road, Mailstop E29, Atlanta, Georgia 30333. Government Programs Addressing Lead and Copper in Potable Water Supplies, Nolton Johnson, Water Resources Management Branch, Georgia Dept of Natural Resources, Environmental Protection Division, Suite 1266, E. Tower, 205 Butler Street, S.E., Atlanta, Georgia 30303. Local Implementation of Federal and State Programs, Michael Patton, Douglasville-Douglas County Water and Sewer Authority. Relating Water Test Results to the Public, Susan Waters, Cobb County - Marietta Water Authority, 680 South Cobb, Marietta, Georgia 30060.Sponsored and Organized by: U.S. Geological Survey, Georgia Department of Natural Resources, The University of Georgia, Georgia State University, Georgia Institute of TechnologyThis book was published by the Institute of Natural Resources, The University of Georgia, Athens, Georgia 30602 with partial funding provided by the U.S. Department of Interior, Geological Survey, through the Georgia Water Research Institute as authorized by the Water Resources Research Act of 1984 (P.L. 98-242). The views and statements advanced in this publication are solely those of the authors and do not represent official views or policies of the University of Georgia or the U.S. Geological Survey or the conference sponsors