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Aminolevulinic acid dehydratase genotype mediates plasma levels of the neurotoxin, 5‐aminolevulinic acid, in lead‐exposed workers
Author(s) -
Sithisarankul Pornchai,
Schwartz Brian S.,
Lee ByungKook,
Kelsey Karl T.,
Strickland Paul T.
Publication year - 1997
Publication title -
american journal of industrial medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.7
H-Index - 104
eISSN - 1097-0274
pISSN - 0271-3586
DOI - 10.1002/(sici)1097-0274(199707)32:1<15::aid-ajim2>3.0.co;2-q
Subject(s) - genotype , dehydratase , zinc protoporphyrin , lead poisoning , medicine , endocrinology , protoporphyrin , creatinine , porphyria , heme , biology , enzyme , biochemistry , gene , porphyrin , psychiatry
The first intermediate substrate in the heme synthetic pathway, 5‐aminolevulinic acid (ALA), is neurotoxic in animal models and may be responsible for some of the adverse neurologic outcomes in lead poisoning and porphyria in adult humans. ALA is a substrate for the enzyme aminolevulinic acid dehydratase (ALAD; EC 4.2.1.24), which is encoded by the ALAD gene containing 2 co‐dominant alleles, 1 and 2. We measured plasma ALA (ALAP) and urinary ALA (ALAU) in 65 Korean lead workers, of whom 44 were homozygous for ALAD1 (ALAD1‐1 genotype) and 21 were heterozygous for ALAD (ALAD1‐2 genotype). ALAP in subjects with the ALAD1‐1 genotype was significantly higher than in those with the ALAD1‐2 genotype (Wilcoxon rank sum test, P = 0.01). No difference between ALAD genotypes was found for age, zinc protoporphyrin (ZPP), blood lead levels (PbB), ALAU, or ALAU adjusted for creatinine. ALAP was significantly correlated with ZPP (Spearman's r = 0.38, P = 0.002) and with PbB (r = 0.34, P = 0.006), and marginally with employment duration (r = 0.22, P = 0.08). ALAP remained significantly elevated ( P = 0.032) in ALAD1‐1 subjects after adjustment for PbB and age by multiple linear regression. These results suggest that ALAD1‐1 subjects respond differently and may be more susceptible than ALAD1‐2 subjects to the ALA‐mediated neurotoxic effects of lead. Am. J. Ind. Med. 32:15‐20, 1997. © 1997 Wiley‐Liss, Inc.