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 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 15-20 |
| Number of pages | 6 |
| Journal | American Journal of Industrial Medicine |
| Volume | 32 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jul 1997 |
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Keywords
- aminolevulinic acid
- blood lead
- genotype
- lead-exposed workers
- neurotoxin
ASJC Scopus subject areas
- Public Health, Environmental and Occupational Health
Cite this
Aminolevulinic acid dehydratase genotype mediates plasma levels of the neurotoxin, 5-aminolevulinic acid, in lead-exposed workers. / Sithisarankul, Pornchai; Schwartz, Brian S; Lee, Byung Kook; Kelsey, Karl T.; Strickland, Paul Timothy.
In: American Journal of Industrial Medicine, Vol. 32, No. 1, 07.1997, p. 15-20.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aminolevulinic acid dehydratase genotype mediates plasma levels of the neurotoxin, 5-aminolevulinic acid, in lead-exposed workers
AU - Sithisarankul, Pornchai
AU - Schwartz, Brian S
AU - Lee, Byung Kook
AU - Kelsey, Karl T.
AU - Strickland, Paul Timothy
PY - 1997/7
Y1 - 1997/7
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 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.
AB - 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.
KW - aminolevulinic acid
KW - blood lead
KW - genotype
KW - lead-exposed workers
KW - neurotoxin
UR - http://www.scopus.com/inward/record.url?scp=0030924965&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030924965&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0274(199707)32:1<15::AID-AJIM2>3.0.CO;2-Q
DO - 10.1002/(SICI)1097-0274(199707)32:1<15::AID-AJIM2>3.0.CO;2-Q
M3 - Article
C2 - 9131207
AN - SCOPUS:0030924965
VL - 32
SP - 15
EP - 20
JO - American Journal of Industrial Medicine
JF - American Journal of Industrial Medicine
SN - 0271-3586
IS - 1
ER -