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

Details

• Alternative Title:
  Environ Health Perspect
• Personal Author:
  Scinicariello, Franco ; Murray, H. Edward ; Moffett, Daphne B. ; Abadin, Henry G. ; Sexton, Mary J. ; Fowler, Bruce A.
• Description:
  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.
  
  
• Subjects:
  Adult ALAD Polymorphism Alleles Biological Markers Blood Pressure Determination Bone And Bones Child Creatinine Environmental Exposure Environmental Pollutants Hemoglobins Humans Lead Meta-analysis Polymorphism, Genetic Porphobilinogen Synthase Protoporphyrins Research

  More +
• Source:
  Environ Health Perspect. 2007; 115(1):35-41.
• Document Type:
  Journal Article
• Volume:
  115
• Issue:
  1
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:770b395c7e53070c8314c20e35009afa0d4c7d2c8f7eb7dd4c6948d4c77950d9
• Download URL:
  https://stacks.cdc.gov/view/cdc/3889/cdc_3889_DS1.pdf
• File Type:
  [PDF - 530.03 KB ]