title: Effect of the delta-aminolevulinate dehydratase polymorphism on the accumulation of lead in bone and blood in lead smelter workers.
abstract: Lead inhibition of the zinc metalloenzyme delta-aminolevulinate dehydratase (ALAD) is one of the most sensitive indicators of blood lead levels. ALAD is polymorphic, with about 20% of Caucasians expressing the rarer ALAD2 allele. Previous studies indicated that this polymorphism may be a genetic factor in lead transport, metabolism, and/or distribution. Whole blood lead, serum lead, and ALAD genotype were determined for 381 lead smelter workers, including 70 workers expressing the ALAD2 allele, whose blood lead elevations were observed for more than 20 years of employment. The same employees demonstrated higher serum lead levels. Using a cumulative blood lead index (CBLI) for each worker, based on individual blood lead histories, and in vivo X-ray fluorescence measurements of bone lead to estimate total lead body burden, the slopes of linear relations of bone lead to CBLI were greater for workers homoallelic for ALAD1, indicating more efficient uptake of lead from blood into bone. This effect was most significant in calcaneus bone and for workers hired since 1977 [ALAD1-1: 0.0528 +/- 0.0028 and ALAD1-2 or 2-2: 0.0355 +/- 0.0031 (P < 0.001)]. Decreased transfer of blood lead into bone in individuals expressing the ALAD2 allele contrasted with increased blood lead. Thus the ALAD genotype affected lead metabolism and potentially modified lead delivery to target organs including the brain; however, the ALAD genotype did not significantly affect the net accumulation of lead in bone.
authors.affiliation: Department of Physics and Astronomy, McMaster University, Hamilton, Ontario, Canada.
authors.forename: D E
authors.initials: DE
authors.lastname: Fleming
authors.forename: D R
authors.initials: DR
authors.lastname: Chettle
authors.forename: J G
authors.initials: JG
authors.lastname: Wetmur
authors.forename: R J
authors.initials: RJ
authors.lastname: Desnick
authors.forename: J P
authors.initials: JP
authors.lastname: Robin
authors.forename: D
authors.initials: D
authors.lastname: Boulay
authors.forename: N S
authors.initials: NS
authors.lastname: Richard
authors.forename: C L
authors.initials: CL
authors.lastname: Gordon
authors.forename: C E
authors.initials: CE
authors.lastname: Webber
mesh_terms: D000595:Amino Acid Sequence; D001842:Bone and Bones / Q000378:metabolism*; D005260:Female; D006801:Humans; D007854:Lead / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008969:Molecular Sequence Data; D016273:Occupational Exposure; D011110:Polymorphism, Genetic / Q000187:drug effects*; D000623:Porphobilinogen Synthase / Q000737:chemistry / Q000235:genetics*; D014018:Tissue Distribution
chemical_list: D007854:Lead; D000623:Porphobilinogen Synthase