EFFECT OF THE DELTA-AMINOLEVULINATE DEHYDRATASE POLYMORPHISM ON THE ACCUMULATION OF LEAD IN BONE AND BLOOD IN LEAD SMELTER WORKERS

Lead inhibition of the zinc metalloenzyme delta-aminolevulinate dehydr atase (ALAD) is one of the most sensitive indicators of blood lead lev els. ALAD is polymorphic, with about 20% of Caucasians expressing the rarer ALAD(2) allele. Previous studies indicated that this polymorphis m may be a genetic factor in lead transport, metabolism, and/or distri bution, Whole blood lead, serum lead, and ALAD genotype were determine d for 381 lead smelter workers, including 70 workers expressing the AL AD(2) allele, whose blood lead elevations were observed for more than 20 years of employment. The same employees demonstrated higher serum l ead levels. Using a cumulative blood lead index (CBLI) for each worker , based on individual blood lead histories, and in vivo X-ray fluoresc ence measurements of bone lead to estimate total lead body burden, the slopes of linear relations of bone lead to CBLI were greater for work ers homoallelic for ALAD(1), indicating more efficient uptake of lead from blood into bone. This effect was most significant in calcaneus bo ne and for workers hired since 1977 [ALAD(1-1): 0.0528+/-0.0028 and AL AD(1-2 or 2-2): 0.0355+/-0.0031 (P<0.001)]. Decreased transfer of bloo d lead into bone in individuals expressing the ALAD(2) allele contrast ed with increased blood lead, Thus the ALAD genotype affected lead met abolism and potentially modified lead delivery to target organs includ ing the brain; however, the ALAD genotype did not significantly affect the net accumulation of lead in bone. (C) 1998 Academic Press.