INTERACTION OF BLOOD LEAD AND DELTA-AMINOLEVULINIC-ACID DEHYDRATASE GENOTYPE ON MARKERS OF HEME-SYNTHESIS AND SPERM PRODUCTION IN LEAD SMELTER WORKERS

'The gene that encodes delta-aminolevulinic acid dehydratase (ALAD) ha s a polymorphism that may modify lead toxicokinetics and ultimately in fluence individual susceptibility to lead poisoning. To evaluate the e ffect of the ALAD polymorphism on lead-mediated outcomes, a cross-sect ional study of male employees from a lead-zinc smelter compared associ ations between blood lead concentration and markers of heme synthesis and semen quality with respect to ALAD genotype. Mate employees were r ecruited via postal questionnaire to donate blood and urine for analys is of blood lead, zinc protoporphyrin (ZPP), urinary coproporphyrin (I ,PU), and ALAD genotype, and semen samples for semen analysis. Of the 134 workers who had ALAD genotypes completed, 114 (85%) were ALAD1-1 ( ALPLD1) and 20 (15%) were ALAD1-2 (ALAD2). The mean blood lead concent rations for ALAD1 and ALAD2 were 23.1 and 28.4 mu g/dl (p = 0.08), res pectively. ZPP/heme ratios were higher in ALAD1 workers (68.6 vs. 57.8 mu mol/mol; p = 0.14), and the slope of the blood lead ZPP linear rel ationship was greater for ALAD1 (2.83 vs. 1.50, P = 0.06). No linear r elationship between CPU and blood lead concentration was observed for either ALAD1 or ALAD2. The associations of blood lead concentration wi th ZPP, CPU, sperm count, and sperm concentration were more evident in workers with the ALAD1 genotype and blood lead concentrations greater than or equal to 40 mu g/dl. The ALAD genetic polymorphism appears to modify the association between blood lead concentration and ZPP. Howe ver, consistent modification of effects were not found for CPU, sperm count, or sperm concentration.