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delta-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system

Zheng, Guang; Tian, Liting; Liang, Yihuai; Broberg Palmgren, Karin LU ; Lei, Lijian; Guo, Weijun; Nilsson, Johan; Bergdahl, Ingvar A.; Skerfving, Staffan LU and Jin, Taiyi (2011) In NeuroToxicology 32(4). p.374-382
Abstract
There is a wide variation in sensitivity to lead (Pb) exposure, which may be due to genetic susceptibility towards Pb. We investigated whether a polymorphism (rs1800435) in the delta-aminolevulinic acid dehydratase (ALAD) gene affected the toxicokinetics and toxicodynamics of Pb. Among 461 Chinese Pb-exposed storage battery and 175 unexposed workers, allele frequencies for the ALAD1 and ALAD2 alleles were 0.968 and 0.032, respectively. The Pb-exposed workers had a higher fraction of the ALAD1-2/2-2 genotype than unexposed workers (7.8% vs. 2.3%, p = 0.01). The Pb levels in blood (B-Pb) and urine (U-Pb) were higher in Pb-exposed workers carrying the AIAD2 allele compared to homozygotes for ALAD1 (median B-Pb: 606 vs. 499 mu g/L; U-Pb: 233... (More)
There is a wide variation in sensitivity to lead (Pb) exposure, which may be due to genetic susceptibility towards Pb. We investigated whether a polymorphism (rs1800435) in the delta-aminolevulinic acid dehydratase (ALAD) gene affected the toxicokinetics and toxicodynamics of Pb. Among 461 Chinese Pb-exposed storage battery and 175 unexposed workers, allele frequencies for the ALAD1 and ALAD2 alleles were 0.968 and 0.032, respectively. The Pb-exposed workers had a higher fraction of the ALAD1-2/2-2 genotype than unexposed workers (7.8% vs. 2.3%, p = 0.01). The Pb levels in blood (B-Pb) and urine (U-Pb) were higher in Pb-exposed workers carrying the AIAD2 allele compared to homozygotes for ALAD1 (median B-Pb: 606 vs. 499 mu g/L; U-Pb: 233 vs. 164 mu g/g creatinine), while there was no statistically significant difference in the unexposed controls (median: 24 vs. 37 mu g/L, and 3.9 vs. 6.4 mu g/g creatinine, respectively). High B-Pb and U-Pb were associated with statistically significantly lower sensory and motor conduction velocities in the median, ulnar and peroneal nerves. At the same B-Pb and U-Pb,ALAD1 homozygotes had lower conduction velocities than the ALAD2 carriers. There were similar trends for toxic effects on haem synthesis (zinc protoporphyrin and haemoglobin in blood) and renal function (albumin and N-acetyl-D-beta-acetylglucosaminidase in urine), but without statistical significance. There was no difference in Pb toxicokinetics and toxicodynamics associated with VDR BsmI polymorphism. Our results show that the ALAD genotype modifies the relationship between Pb and its toxic effects on the peripheral nervous system. This must be considered in the assessment of risks at Pb exposure. (C) 2011 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lead, ALAD, Gene-environment interaction, Peripheral nervous system, Haem synthesis, Kidney
in
NeuroToxicology
volume
32
issue
4
pages
374 - 382
publisher
Elsevier
external identifiers
  • wos:000291762600003
  • scopus:79955098977
ISSN
1872-9711
DOI
10.1016/j.neuro.2011.03.006
language
English
LU publication?
yes
id
3249e629-6a72-43f6-835b-0e791f8fb338 (old id 2052522)
date added to LUP
2011-08-02 09:01:21
date last changed
2017-05-14 04:04:46
@article{3249e629-6a72-43f6-835b-0e791f8fb338,
  abstract     = {There is a wide variation in sensitivity to lead (Pb) exposure, which may be due to genetic susceptibility towards Pb. We investigated whether a polymorphism (rs1800435) in the delta-aminolevulinic acid dehydratase (ALAD) gene affected the toxicokinetics and toxicodynamics of Pb. Among 461 Chinese Pb-exposed storage battery and 175 unexposed workers, allele frequencies for the ALAD1 and ALAD2 alleles were 0.968 and 0.032, respectively. The Pb-exposed workers had a higher fraction of the ALAD1-2/2-2 genotype than unexposed workers (7.8% vs. 2.3%, p = 0.01). The Pb levels in blood (B-Pb) and urine (U-Pb) were higher in Pb-exposed workers carrying the AIAD2 allele compared to homozygotes for ALAD1 (median B-Pb: 606 vs. 499 mu g/L; U-Pb: 233 vs. 164 mu g/g creatinine), while there was no statistically significant difference in the unexposed controls (median: 24 vs. 37 mu g/L, and 3.9 vs. 6.4 mu g/g creatinine, respectively). High B-Pb and U-Pb were associated with statistically significantly lower sensory and motor conduction velocities in the median, ulnar and peroneal nerves. At the same B-Pb and U-Pb,ALAD1 homozygotes had lower conduction velocities than the ALAD2 carriers. There were similar trends for toxic effects on haem synthesis (zinc protoporphyrin and haemoglobin in blood) and renal function (albumin and N-acetyl-D-beta-acetylglucosaminidase in urine), but without statistical significance. There was no difference in Pb toxicokinetics and toxicodynamics associated with VDR BsmI polymorphism. Our results show that the ALAD genotype modifies the relationship between Pb and its toxic effects on the peripheral nervous system. This must be considered in the assessment of risks at Pb exposure. (C) 2011 Elsevier Inc. All rights reserved.},
  author       = {Zheng, Guang and Tian, Liting and Liang, Yihuai and Broberg Palmgren, Karin and Lei, Lijian and Guo, Weijun and Nilsson, Johan and Bergdahl, Ingvar A. and Skerfving, Staffan and Jin, Taiyi},
  issn         = {1872-9711},
  keyword      = {Lead,ALAD,Gene-environment interaction,Peripheral nervous system,Haem synthesis,Kidney},
  language     = {eng},
  number       = {4},
  pages        = {374--382},
  publisher    = {Elsevier},
  series       = {NeuroToxicology},
  title        = {delta-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system},
  url          = {http://dx.doi.org/10.1016/j.neuro.2011.03.006},
  volume       = {32},
  year         = {2011},
}