Tags

Type your tag names separated by a space and hit enter

δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system.
Neurotoxicology 2011; 32(4):374-82N

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 δ-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 ALAD2 allele compared to homozygotes for ALAD1 (median B-Pb: 606 vs. 499 μg/L; U-Pb: 233 vs. 164 μg/g creatinine), while there was no statistically significant difference in the unexposed controls (median: 24 vs. 37 μg/L, and 3.9 vs. 6.4μg/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-β-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.

Authors+Show Affiliations

Department of Occupational Health and Toxicology, School of Public Health, Fudan University, Shanghai, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21439310

Citation

Zheng, Guang, et al. "Δ-Aminolevulinic Acid Dehydratase Genotype Predicts Toxic Effects of Lead On Workers' Peripheral Nervous System." Neurotoxicology, vol. 32, no. 4, 2011, pp. 374-82.
Zheng G, Tian L, Liang Y, et al. Δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system. Neurotoxicology. 2011;32(4):374-82.
Zheng, G., Tian, L., Liang, Y., Broberg, K., Lei, L., Guo, W., ... Jin, T. (2011). Δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system. Neurotoxicology, 32(4), pp. 374-82. doi:10.1016/j.neuro.2011.03.006.
Zheng G, et al. Δ-Aminolevulinic Acid Dehydratase Genotype Predicts Toxic Effects of Lead On Workers' Peripheral Nervous System. Neurotoxicology. 2011;32(4):374-82. PubMed PMID: 21439310.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - δ-Aminolevulinic acid dehydratase genotype predicts toxic effects of lead on workers' peripheral nervous system. AU - Zheng,Guang, AU - Tian,Liting, AU - Liang,Yihuai, AU - Broberg,Karin, AU - Lei,Lijian, AU - Guo,Weijun, AU - Nilsson,Johan, AU - Bergdahl,Ingvar A, AU - Skerfving,Staffan, AU - Jin,Taiyi, Y1 - 2011/03/23/ PY - 2011/02/06/received PY - 2011/03/15/revised PY - 2011/03/15/accepted PY - 2011/3/29/entrez PY - 2011/3/29/pubmed PY - 2012/4/24/medline SP - 374 EP - 82 JF - Neurotoxicology JO - Neurotoxicology VL - 32 IS - 4 N2 - 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 δ-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 ALAD2 allele compared to homozygotes for ALAD1 (median B-Pb: 606 vs. 499 μg/L; U-Pb: 233 vs. 164 μg/g creatinine), while there was no statistically significant difference in the unexposed controls (median: 24 vs. 37 μg/L, and 3.9 vs. 6.4μg/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-β-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. SN - 1872-9711 UR - https://www.unboundmedicine.com/medline/citation/21439310/δ_Aminolevulinic_acid_dehydratase_genotype_predicts_toxic_effects_of_lead_on_workers'_peripheral_nervous_system_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-813X(11)00053-2 DB - PRIME DP - Unbound Medicine ER -