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Aminolevulinic acid dehydratase genotype mediates plasma levels of the neurotoxin, 5-aminolevulinic acid, in lead-exposed workers.
Am J Ind Med. 1997 Jul; 32(1):15-20.AJ

Abstract

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 ALADI (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.

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Authors+Show Affiliations

Sithisarankul P
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD 21205, USA.
Schwartz BS
No affiliation info available
Lee BK
No affiliation info available
Kelsey KT
No affiliation info available
Strickland PT
No affiliation info available

MeSH

AdultAminolevulinic AcidGenotypeHumansKoreaLeadMaleMiddle AgedOccupational ExposurePorphobilinogen Synthase

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9131207

Citation

Sithisarankul, P, et al. "Aminolevulinic Acid Dehydratase Genotype Mediates Plasma Levels of the Neurotoxin, 5-aminolevulinic Acid, in Lead-exposed Workers." American Journal of Industrial Medicine, vol. 32, no. 1, 1997, pp. 15-20.
Sithisarankul P, Schwartz BS, Lee BK, et al. Aminolevulinic acid dehydratase genotype mediates plasma levels of the neurotoxin, 5-aminolevulinic acid, in lead-exposed workers. Am J Ind Med. 1997;32(1):15-20.
Sithisarankul, P., Schwartz, B. S., Lee, B. K., Kelsey, K. T., & Strickland, P. T. (1997). Aminolevulinic acid dehydratase genotype mediates plasma levels of the neurotoxin, 5-aminolevulinic acid, in lead-exposed workers. American Journal of Industrial Medicine, 32(1), 15-20.
Sithisarankul P, et al. Aminolevulinic Acid Dehydratase Genotype Mediates Plasma Levels of the Neurotoxin, 5-aminolevulinic Acid, in Lead-exposed Workers. Am J Ind Med. 1997;32(1):15-20. PubMed PMID: 9131207.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aminolevulinic acid dehydratase genotype mediates plasma levels of the neurotoxin, 5-aminolevulinic acid, in lead-exposed workers. AU - Sithisarankul,P, AU - Schwartz,B S, AU - Lee,B K, AU - Kelsey,K T, AU - Strickland,P T, PY - 1997/7/1/pubmed PY - 2000/6/20/medline PY - 1997/7/1/entrez SP - 15 EP - 20 JF - American journal of industrial medicine JO - Am J Ind Med VL - 32 IS - 1 N2 - 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 ALADI (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. SN - 0271-3586 UR - https://www.unboundmedicine.com/medline/citation/9131207/Aminolevulinic_acid_dehydratase_genotype_mediates_plasma_levels_of_the_neurotoxin_5_aminolevulinic_acid_in_lead_exposed_workers_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0271-3586&date=1997&volume=32&issue=1&spage=15 DB - PRIME DP - Unbound Medicine ER -