Polymorphisms of delta-aminolevulinic acid dehydratase (ALAD) and peptide transporter 2 (PEPT2) genes in children with low-level lead exposure
Low-level lead exposure during early childhood has long been associated with altered neurocognitive development and diminished cognitive functions. Over nine thousand U.S. industrial facilities annually emit significant amounts of lead, creating exposure risk particularly for minority children. The mechanisms by which low-level lead exerts neurotoxic effects are poorly understood. Once absorbed, the only intervention is source removal, thus primary prevention is key. Genetic biomarkers could provide an efficient means of identifying children at greatest risk. Common functional variants of genes that alter lead’s neurotoxic potential have been identified and include delta-aminolevulinic acid dehydratase (ALAD2) and peptide transporter 2 (PEPT2*2). These polymorphisms have not been examined previously in Hispanic minority samples, or with regard to lowest level lead exposure. In 116 children of Mexican-American/Hispanic descent residing in zip codes previously designated as “high risk” for lead exposure (mean age = 8.1, SD = 1.9), blood lead level was measured at three time points over a three month period and averaged. DNA extraction was completed using buccal swab samples. The frequencies of the ALAD2 and PEPT2*2 polymorphisms observed in this sample closely approximated those previously reported for Anglo, European and Asian samples. As compared to children heterozygous for the PEPT2*2 polymorphism, and without the PEPT2*2 polymorphism, the geometric mean blood lead level of children homozygous for the PEPT2*2 polymorphism was significantly higher. In contrast to past studies, mean blood lead level of children heterozygous and homozygous for the ALAD2 polymorphism in this sample did not differ from that of children without the ALAD2 polymorphism. Higher blood lead burden in children with the PEPT2*2 mutation may suggest that this common genetic variant is a biomarker of increased vulnerability to the neurotoxic effects of lowest level lead exposure.
Christina Sobin, Marisela Gutierrez, and Heather Alterio. "Polymorphisms of delta-aminolevulinic acid dehydratase (ALAD) and peptide transporter 2 (PEPT2) genes in children with low-level lead exposure" Neurotoxicology in press (2009).
Available at: http://works.bepress.com/christina_sobin/15