Facultad de Medicina, Universidad Ju arez del Estado de Durango, LaSalle 1 y Sixto Ugalde S/N, Col. Revolución, Gómez Palacio, Durango, 35050, México.
Toxicol Mech Methods. 2006;16(1):41-7. doi: 10.1080/15376520500191946.
The implications of delta-aminolevulinic acid dehydratase (ALAD) polymorphism for lead kinetics and toxicity have been mainly studied in occupationally exposed adults. Therefore, our purpose was to evaluate the distribution of ALAD genotype and its association with biomarkers of exposure (PbB levels) and effect (Blood ZPP) among children living in a smelter community in Mexico. We recruited 569 children from nine elementary schools close to a smelter site. PbB was determined by electrothermal atomic absorption spectrometry. A polymerase chain reaction (PCR)-based protocol was used for ALAD genotyping. Zinc protoporphyrin (ZPP) in blood was measured by direct fluorometry. Most children (93.15%) were homozygous for ALAD (1-1), 6.67% were heterozygous for ALAD for (1-2), and one child was homozygous for ALAD (2-2). There was an increased proportion of ALAD (1-2/2-2) genotype with respect to PbB levels. The ZPP geometric mean was slightly higher in ALAD (1-1) genotype children (63.48 mu mol ZPP/mol Hb) than in those having the ALAD-2 genotype (58.22 mu mol ZPP/mol Hb; p = 0.051). Linear and quadratic models showed significant relationships between ZPP and PbB. A significant increase in the odds ratio (OR) for the effect of lead exposure on ZPP levels was observed for ALAD (1-1) children having PbB values above 20 mu g/dL, as compared to those having PbB levels below 10 mu g/dL (OR = 2.95, 95% CI = 1.45-5.97; p = 0.003), whereas no significant increases were observed for the ALAD (1-2/2-2) children. In summary, our results suggest that heme biosynthesis was less affected in ALAD (1-2/2-2) lead-exposed children than in those carrying the ALAD (1-1) genotype.
δ-氨基酮戊酸脱水酶(ALAD)多态性对铅动力学和毒性的影响主要在职业暴露的成年人中进行了研究。因此,我们的目的是评估在墨西哥一家冶炼厂附近社区生活的儿童中 ALAD 基因型的分布及其与暴露生物标志物(PbB 水平)和效应(血 ZPP)的关系。我们从靠近冶炼厂的九所小学招募了 569 名儿童。采用电热原子吸收光谱法测定 PbB。使用聚合酶链反应(PCR)-基于方案用于 ALAD 基因分型。通过直接荧光法测量血液中的锌原卟啉(ZPP)。大多数儿童(93.15%)为 ALAD(1-1)纯合子,6.67%为 ALAD(1-2)杂合子,一名儿童为 ALAD(2-2)纯合子。ALAD(1-2/2-2)基因型的比例随着 PbB 水平的升高而增加。ZPP 几何平均值在 ALAD(1-1)基因型儿童中略高(63.48μmol ZPP/mol Hb),而在具有 ALAD-2 基因型的儿童中略低(58.22μmol ZPP/mol Hb;p=0.051)。线性和二次模型显示 ZPP 与 PbB 之间存在显著关系。对于 PbB 值高于 20μg/dL 的 ALAD(1-1)儿童,与 PbB 水平低于 10μg/dL 的儿童相比,铅暴露对 ZPP 水平的影响的比值比(OR)显著增加(OR=2.95,95%CI=1.45-5.97;p=0.003),而对于 ALAD(1-2/2-2)儿童则没有观察到显著增加。总之,我们的结果表明,在携带 ALAD(1-1)基因型的铅暴露儿童中,血红素生物合成受影响较小,而在携带 ALAD(1-2/2-2)基因型的儿童中受影响较大。