Delta-aminolevulinic Acid dehydratase genotype and its relationship with blood lead and zinc protoporphyrin levels in lead-exposed children living in a smelter community in northern Mexico.Toxicol Mech Methods. 2006; 16(1):41-7.TM
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.