A polymorphism in the delta-aminolevulinic acid dehydratase gene modifies plasma/whole blood lead ratio
- 197 Downloads
Delta aminolevulinic acid dehydratase (ALAD) plays an important role in lead poisoning. This study was carried out to examine the effects of ALAD gene polymorphism (G177C) on %Pb-P(plasma lead)/Pb-B(whole blood) ratio in 142 subjects environmentally exposed to lead. Genotypes for the ALAD G177C polymorphism were determined by PCR and restriction fragment length digestion. Pb-P and Pb-B were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. The allele frequencies for ALAD1 and ALAD2 alleles were 0.897 and 0.103, respectively. We combined both ALAD 1-2 and ALAD 2-2 genotypes together (ALAD 1-2/2-2 group) and compared with the ALAD 1-1 genotype group. While no significant differences were found in Pb-B, subjects from the ALAD 1-2/2-2 genotype group presented significantly higher Pb-P concentrations and %Pb-P/Pb-B ratios (0.89±0.07 μg/l, and 1.45±0.10%, respectively) when compared with subjects from the ALAD 1-1 genotype group (0.44±0.05 μg/l, and 0.48±0.02, respectively; both P<0.0001). The higher %Pb-P/Pb-B ratios in carriers of the ALAD-2 allele compared with noncarriers indicate that ALAD 1-2/2-2 subjects are probably at increased health risks associated with lead exposure.
KeywordsALAD polymorphism Delta aminolevulinic acid dehydratase Lead toxicology Plasma lead Whole blood lead Plasma/whole blood lead ratio
This study was supported by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP), Coordenadoria de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Conselho Nacional de Desenvolvimento e Cientifico e Tecnológico (CNPq).
- Barbosa F Jr, Tanus-Santos JE, Gerlach RF, Parsons PJ (2005) Current needs and limitations on the use of biomarkers of internal dose to diagnose lead exposure. Environ Health Perspect 113:1669–1674Google Scholar
- Barbosa F Jr, Sandrim VC, Uzuelli JA, Gerlach RF, Tanus-Santos JE (2006) eNOS genotype-dependent correlation between whole blood lead and plasma nitric oxide products concentrations. Nitric Oxide (in press)Google Scholar
- Perez-Bravo F, Ruz M, Moran-Jimenez MJ, Olivares M, Rebolledo A, Codoceo J, Sepulveda V, Jenkin A, Santos JL, Fontanellas A (2004) Association between aminolevulinate dehydrase genotypes and blood lead levels in children from a lead-contaminated area in Antofagasta, Chile. Arch Environ Contam Toxicol 47:276–280PubMedCrossRefGoogle Scholar
- Wetmur JG, Kaya AH, Plewinska M, Desnick RJ (1991a) Molecular characterization of the human delta-aminolevulinate dehydratase 2 (ALAD2) allele: implications for molecular screening of individuals for genetic susceptibility to lead poisoning. Am J Hum Genet 49:757–763Google Scholar