Associations of δ-Aminolevulinic Acid Dehydratase Genotype with Plant, Exposure Duration, and Blood Lead and Zinc Protoporphyrin Levels in Korean Lead Workers

Abstract

Previous studies have suggested that polymorphisms in delta-aminolevulinic acid dehydratase (ALAD), a heme synthetic enzyme, may be associated with differences in blood lead levels, perhaps due to differential binding of lead in erythrocytes. The authors examined associations of ALAD genotype with blood lead and zinc protoporphyrin (ZPP) levels, exposure duration, sex, and plant in 308 currently exposed lead workers in three lead storage battery manufacturing plants in the Republic of Korea in 1993. The overall prevalence of the variant allele, ALAD2, was 11%, but prevalence varied by plant (p = 0.02: 8.6% in plant A, 20% in plant B, and 22% in plant C). While ALAD2 was not associated with mean blood lead levels, the allele was associated with blood lead levels greater than or equal to 40 micrograms/dl (crude odds ratio (OR) = 2.6, 95% confidence interval (CI) 1.1-6.3; adjusted OR = 2.3, 95% CI 0.8-6.2, with adjustment for sex, plant, and exposure duration) and with exposure durations greater than 6 years (adjusted OR = 2.5, 95% CI 1.2-5.4, with adjustment for blood lead, sex, and plant). Among workers in plant C, the highest exposure plant, ALAD2 was associated with lower ZPP levels when controlling for blood lead levels. These data suggest that lead toxicokinetics may be modified by ALAD genotype and that ALAD2 may be protective for the health effects of lead. ALAD genotype also appears to have been a selection factor for current lead exposure status in the studied workers.

A study on ALAD (G177C and T168C) and MGP (T-138C) gene polymorphisms associated with lead exposure in subjects from Saudi Arabia

“…In is important to note that the length of exposure to lead, working hours and poor nutritional status may have contributed to these results in subjects with high BLL. Our results indicate that ALAD 1-2/22 variants may not play a substantial role in modulating BLL at higher exposure levels (Schwartz et al, 1995).…”

“…At the molecular level, lead displaces a zinc ion at the metal binding site (not the active site) producing inhibition through a change in the enzyme's quaternary structure. This inhibition of ALAD results in the buildup of aminolevulinic acid, detectable in the plasma and urine at BLL less than 10 µg/dl (Schwartz et al, 1995). Thus, ALAD enzyme plays a major role in response to metal poisoning caused by lead, which strongly inhibits ALAD stoichiometrically (Wetmur et al, 1991a;Wetmur et al, 1991b;Schwartz et al, 1995).…”

“…This inhibition of ALAD results in the buildup of aminolevulinic acid, detectable in the plasma and urine at BLL less than 10 µg/dl (Schwartz et al, 1995). Thus, ALAD enzyme plays a major role in response to metal poisoning caused by lead, which strongly inhibits ALAD stoichiometrically (Wetmur et al, 1991a;Wetmur et al, 1991b;Schwartz et al, 1995). It is important to note that the gene coding for ALAD enzyme (chromosome 9q34) is polymorphic in nature; the ALADG177C polymorphism yields two co-dominant alleles, ALAD-1 and ALAD-2 which have been implicated in susceptibility to lead toxicity.…”

“…Studies have suggested that carriers of the ALAD2 allele have higher BLL than ALAD1 subjects and thus are more susceptible to lead toxicity (Wetmur et al, 1991b;Kelada et al, 2001;Onalaja and Claudio, 2000;ATSDR, 2006). Some authors suggest that the enhanced capacity of ALAD2 to bind lead may confer resistance to its harmful effects because subjects with ALAD2 may have less bioavailable lead (Schwartz et al, 1995). Genotype frequencies vary by geography and race (Onalaja and Claudio, 2000).…”

No ALAD Polymorphism in Bank Vole Populations from Unpolluted and Lead-Zinc Polluted Areas in Poland

“…Most human research discusses people with an occupational exposure to lead. SCHWARTZ et al (1995) showed that ALAD2 is more frequent among workers exposed for over 6 years compared to those exposed for less than six years. This may suggest that ALAD2 is favourable in coping with lead intoxication.…”