| Lead and ?-Aminolevulinic Acid Dehydratase Polymorphism: Where Does It Lead? A Meta-Analysis Franco Scinicariello,1 H. Edward Murray,1 Daphne B. Moffett,1 Henry G. Abadin,1 Mary J. Sexton,2 and Bruce A. Fowler1 1Division of Toxicology and Environmental Medicine, Agency for Toxic Substances and Disease Registry, Centers of Disease Control and Prevention, Atlanta, Georgia, USA; 2Epidemiology Consultant, Atlanta, Georgia, USA Abstract
Background: Lead poisoning affects many organs in the body. Lead inhibits  -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. Key words: ALAD polymorphism, lead, meta-analysis. Environ Health Perspect 115:35–41 (2007) . doi:10.1289/ehp.9448 available via http://dx.doi.org/ [Online 15 September 2006]
Address correspondence to F. Scinicariello, Division of Toxicology and Environmental Medicine, ATSDR, CDC, MS F-32, 4770 Buford Hwy., Atlanta, GA 30341 USA. Telephone: (770) 488-3331. Fax: (770) 488-4178. E-mail: fes6@cdc.gov This project was supported under a cooperative agreement form the CDC through the Association of Teachers of Preventive Medicine. Franco Scinicariello is a recipient of an ATPM (Association of Teachers of Preventive Medicine) Career Development Award. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the ATSDR. The authors declare they have no competing financial interests. Received 22 June 2006 ; accepted 15 September 2006.
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