Association between aminolevulinate dehydrase genotypes and blood lead levels in children from a lead-contaminated area in Antofagasta, Chile.

Childhood environmental lead exposure in the city of Antofagasta, Chile, was generated by the accumulation of recently removed lead stores derived from mining activities for a long period of time. Susceptibility to harmful lead effects may be associated with polymorphisms of delta-aminolevulinic acid dehydratase (ALAD) because of the differential binding of lead to the codified proteins. We assessed the associations and possible interactions among the following variables: blood lead levels, ALAD genotypes, and distance to the source of lead contamination in Chilean children exposed to lead contamination in Antofagasta, Chile. Ninety-three children were recruited from schools located near a lead- contaminated area. Lead blood levels were measured by atomic absorption spectrophotometry. ALAD genotypes were determined by polymerase chain reaction and restriction fragment-length polymorphism analysis. The frequency of the ALAD-2 allele was estimated at 0.054. Children with the ALAD-2 genotype had higher blood lead levels than noncarriers (p = 0.06). As expected, blood lead levels were inversely correlated with the distance from lead stores. Interestingly, ALAD-2 carriers were more frequent within the area defined by a distance of 200 m from lead deposits (27%) than in areas >200 m (5%) away. Children living within a maximum distance of 200 m from the lead stores showed higher blood lead levels in ALAD-2 carriers (geometric mean = 16.4 microg/dl, range 6 to 27) than in noncarriers (geometric mean = 12.1 microg/dl, range 0 to 26) without achieving statistical significance (p = 0.13). A trend for higher blood lead levels in ALAD-2 carriers compared with ALAD-1 homozygous children has been observed. Because ALAD-2 frequency was higher in subjects living within 200 m from the lead deposits, we hypothesized that a long-term selective pressure against the presence of the ALAD-1 allele is the cause of the overrepresentation of the ALAD-2 allele in children living in proximity to the recently removed lead stores.