δ-Aminolevulinic acid dehydratase single nucleotide polymorphism 2 and peptide transporter 2*2 haplotype may differentially mediate lead exposure in male children.

Child low-level lead (Pb) exposure is an unresolved public health problem and an unaddressed child health disparity. Particularly in cases of low-level exposure, source removal can be impossible to accomplish, and the only practical strategy for reducing risk may be primary prevention. Genetic biomarkers of increased neurotoxic risk could help to identify small subgroups of children for early intervention. Previous studies have suggested that, by way of a distinct mechanism, δ-aminolevulinic acid dehydratase single nucleotide polymorphism 2 (ALAD(2)) and/or peptide transporter 22 haplotype (hPEPT22) increase Pb blood burden in children. Studies have not yet examined whether sex mediates the effects of genotype on blood Pb burden. Also, previous studies have not included blood iron (Fe) level in their analyses. Blood and cheek cell samples were obtained from 306 minority children, ages 5.1 to 12.9 years. (208)Pb and (56)Fe levels were determined with inductively coupled plasma-mass spectrometry. General linear model analyses were used to examine differences in Pb blood burden by genotype and sex while controlling for blood Fe level. The sample geometric mean Pb level was 2.75 μg/dl. Pb blood burden was differentially higher in ALAD(2) heterozygous boys and hPEPT22 homozygous boys. These results suggest that the effect of ALAD(2) and hPEPT22 on Pb blood burden may be sexually dimorphic. ALAD(2) and hPEPT2*2 may be novel biomarkers of health and mental health risks in male children exposed to low levels of Pb.