Border Biomedical Research Center, Toxicology Project and Laboratory of Neurocognitive Genetics and Developmental Neurocognition, Department of Psychology, University of Texas, El Paso, El Paso, TX 79968, USA.
Neurotoxicology. 2009 Nov;30(6):881-7. doi: 10.1016/j.neuro.2009.08.006. Epub 2009 Aug 31.
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 (ALAD(2)) and peptide transporter 2 (PEPT22). 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, S.D.=1.9), blood lead level was measured at three time points over a 3-month period and averaged. DNA extraction was completed using buccal swab samples. The frequencies of the ALAD(2) and PEPT22 polymorphisms observed in this sample closely approximated those previously reported for Anglo, European and Asian samples. As compared to children heterozygous for the PEPT22 polymorphism, and without the PEPT22 polymorphism, the geometric mean blood lead level of children homozygous for the PEPT22 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 PEPT22 mutation may suggest that this common genetic variant is a biomarker of increased vulnerability to the neurotoxic effects of lowest level lead exposure.
儿童早期的低水平铅暴露长期以来一直与神经认知发育改变和认知功能减退有关。每年有超过 9000 家美国工业设施大量排放铅，这尤其给少数族裔儿童带来了暴露风险。低水平铅发挥神经毒性作用的机制尚未得到充分理解。一旦被吸收，唯一的干预措施就是去除源头，因此，初级预防是关键。遗传生物标志物可以提供一种有效手段来识别风险最大的儿童。已经确定了改变铅神经毒性潜力的基因常见功能变体，包括 δ-氨基酮戊酸脱水酶 (ALAD(2)) 和肽转运蛋白 2 (PEPT22)。这些多态性以前没有在西班牙裔少数族裔样本中或最低水平铅暴露的情况下进行过研究。在居住在以前被指定为铅暴露“高风险”的邮政编码（平均年龄=8.1，标准差=1.9）的 116 名墨西哥裔/西班牙裔儿童中，在 3 个月的时间内分三个时间点测量了血铅水平，并取平均值。使用口腔拭子样本完成 DNA 提取。在这个样本中观察到的 ALAD(2)和 PEPT22 多态性的频率与以前报道的盎格鲁、欧洲和亚洲样本非常接近。与杂合子 PEPT22 多态性且没有 PEPT22 多态性的儿童相比，纯合子 PEPT22 多态性的儿童血铅几何均数显著更高。与过去的研究相反，在这个样本中，ALAD2 多态性杂合子和纯合子的儿童的平均血铅水平与没有 ALAD2 多态性的儿童没有差异。携带 PEPT22 突变的儿童血铅负荷更高，这可能表明这种常见的遗传变体是对最低水平铅暴露的神经毒性作用易感性增加的生物标志物。
