Lead and delta-aminolevulinic acid dehydratase polymorphism: where does it lead? A meta-analysis.
BACKGROUND
Lead poisoning affects many organs in the body. Lead inhibits delta-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.


METHODS
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.


METHODS
Sample sizes, means, and standard deviations were extracted for the genotype groups.


RESULTS
There was a statistically significant association between ALAD2 carriers and higher BLL in lead-exposed workers (weighted mean differences of 1.93 microg/dL). There was no association with ALAD carrier status among environmentally exposed adults with BLLs < 10 microg/dL. ALAD2 carriers were potentially protected against adverse hemapoietic effects (ZPP and hemoglobin levels), perhaps because of decreased lead bioavailability to heme pathway enzymes.


CONCLUSIONS
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.
Scinicariello
Franco
F
Division of Toxicology and Environmental Medicine, Agency for Toxic Substances and Disease Registry, Centers of Disease Control and Prevention, Atlanta, Georgia 30341, USA. fes6@cdc.gov
Murray
H Edward
HE
Moffett
Daphne B
DB
Abadin
Henry G
HG
Sexton
Mary J
MJ
Fowler
Bruce A
BA
D000328:Adult; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D001795:Blood Pressure Determination; D001842:Bone and Bones / Q000737:chemistry; D002648:Child; D003404:Creatinine / Q000097:blood; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000032:analysis / Q000097:blood* / Q000633:toxicity; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007854:Lead / Q000032:analysis / Q000097:blood* / Q000633:toxicity; D011110:Polymorphism, Genetic; D000623:Porphobilinogen Synthase / Q000235:genetics*; D011524:Protoporphyrins / Q000097:blood
D015415:Biomarkers; D004785:Environmental Pollutants; D006454:Hemoglobins; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D007854:Lead; D003404:Creatinine; D000623:Porphobilinogen Synthase