Delta-aminolevulinic acid dehydratase polymorphism: influence on lead levels and kidney function in humans.
Delta-aminolevulinic acid dehydratase (ALAD) polymorphism has been reported to modify lead pharmacokinetics (i.e., individuals who express the ALAD2 allele [ALAD2 subjects] have higher blood lead levels than homozygotes for the ALAD1 allele [ALAD1 subjects]). In our study of 89 lead-exposed workers (7 ALAD2 homozygotes or heterozygotes) and 34 unexposed workers (10 ALAD2 heterozygotes), concentrations of urinary calcium and creatinine were lower in ALAD2 subjects than in ALAD1 subjects (respective medians: calcium--78 mg/l versus 185 mg/l, p = .003; creatinine--11.2 mmol/l versus 14.9 mmol/l, p = .008). No association was found between ALAD genotype and blood lead levels or bone lead levels. However, expression of the ALAD2 allele occurred less frequently among lead-exposed workers than in unexposed controls. The results indicated the presence of ALAD allele-specific differences in kidney function, as well as a possible genetic healthy-worker selection.
Bergdahl
I A
IA
Department of Occupational and Environmental Medicine, University Hospital, Lund, Sweden.
Gerhardsson
L
L
Schütz
A
A
Desnick
R J
RJ
Wetmur
J G
JG
Skerfving
S
S
D000483:Alleles; D002118:Calcium / Q000652:urine; D003404:Creatinine / Q000652:urine; D005838:Genotype; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007854:Lead / Q000009:adverse effects* / Q000032:analysis; D008669:Metallurgy; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis / Q000706:statistics & numerical data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D000623:Porphobilinogen Synthase / Q000235:genetics*; D018709:Statistics, Nonparametric
D007854:Lead; D003404:Creatinine; D000623:Porphobilinogen Synthase; D002118:Calcium