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Associations of uric acid with polymorphisms in the delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers.
Environ Health Perspect 2005; 113(11):1509-15EH

Abstract

Recent research suggests that uric acid may be nephrotoxic at lower levels than previously recognized and that it may be one mechanism for lead-related nephrotoxicity. Therefore, in understanding mechanisms for lead-related nephrotoxicity, it would be of value to determine whether genetic polymorphisms that are associated with renal outcomes in lead workers and/or modify associations between lead dose and renal function are also associated with uric acid and/or modify associations between lead dose and uric acid. We analyzed data on three such genetic polymorphisms: delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR). Mean (+/- SD) tibia, blood, and dimercaptosuccinic acid-chelatable lead levels were 37.2 +/- 40.4 microg/g bone mineral, 32.0+/- 15.0 g/dL, and 0.77+/- 0.86 microg/mg creatinine, respectively, in 798 current and former lead workers. Participants with the eNOSAsp allele had lower mean serum uric acid compared with those with the Glu/Glu genotype. Among older workers (age > or = median of 40.6 years), ALAD genotype modified associations between lead dose and uric acid levels. Higher lead dose was significantly associated with higher uric acid in workers with the ALAD1-1 genotype; associations were in the opposite direction in participants with the variant ALAD1-2 genotype. In contrast, higher tibia lead was associated with higher uric acid in those with the variant VDRB allele; however, modification was dependent on participants with the bb genotype and high tibia lead levels. We conclude that genetic polymorphisms may modify uric acid mediation of lead-related adverse renal effects.

Authors+Show Affiliations

Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

16263504

Citation

Weaver, Virginia M., et al. "Associations of Uric Acid With Polymorphisms in the Delta-aminolevulinic Acid Dehydratase, Vitamin D Receptor, and Nitric Oxide Synthase Genes in Korean Lead Workers." Environmental Health Perspectives, vol. 113, no. 11, 2005, pp. 1509-15.
Weaver VM, Schwartz BS, Jaar BG, et al. Associations of uric acid with polymorphisms in the delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers. Environ Health Perspect. 2005;113(11):1509-15.
Weaver, V. M., Schwartz, B. S., Jaar, B. G., Ahn, K. D., Todd, A. C., Lee, S. S., ... Lee, B. K. (2005). Associations of uric acid with polymorphisms in the delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers. Environmental Health Perspectives, 113(11), pp. 1509-15.
Weaver VM, et al. Associations of Uric Acid With Polymorphisms in the Delta-aminolevulinic Acid Dehydratase, Vitamin D Receptor, and Nitric Oxide Synthase Genes in Korean Lead Workers. Environ Health Perspect. 2005;113(11):1509-15. PubMed PMID: 16263504.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Associations of uric acid with polymorphisms in the delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers. AU - Weaver,Virginia M, AU - Schwartz,Brian S, AU - Jaar,Bernard G, AU - Ahn,Kyu-Dong, AU - Todd,Andrew C, AU - Lee,Sung-Soo, AU - Kelsey,Karl T, AU - Silbergeld,Ellen K, AU - Lustberg,Mark E, AU - Parsons,Patrick J, AU - Wen,Jiayu, AU - Lee,Byung-Kook, PY - 2005/11/3/pubmed PY - 2006/1/27/medline PY - 2005/11/3/entrez SP - 1509 EP - 15 JF - Environmental health perspectives JO - Environ. Health Perspect. VL - 113 IS - 11 N2 - Recent research suggests that uric acid may be nephrotoxic at lower levels than previously recognized and that it may be one mechanism for lead-related nephrotoxicity. Therefore, in understanding mechanisms for lead-related nephrotoxicity, it would be of value to determine whether genetic polymorphisms that are associated with renal outcomes in lead workers and/or modify associations between lead dose and renal function are also associated with uric acid and/or modify associations between lead dose and uric acid. We analyzed data on three such genetic polymorphisms: delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR). Mean (+/- SD) tibia, blood, and dimercaptosuccinic acid-chelatable lead levels were 37.2 +/- 40.4 microg/g bone mineral, 32.0+/- 15.0 g/dL, and 0.77+/- 0.86 microg/mg creatinine, respectively, in 798 current and former lead workers. Participants with the eNOSAsp allele had lower mean serum uric acid compared with those with the Glu/Glu genotype. Among older workers (age > or = median of 40.6 years), ALAD genotype modified associations between lead dose and uric acid levels. Higher lead dose was significantly associated with higher uric acid in workers with the ALAD1-1 genotype; associations were in the opposite direction in participants with the variant ALAD1-2 genotype. In contrast, higher tibia lead was associated with higher uric acid in those with the variant VDRB allele; however, modification was dependent on participants with the bb genotype and high tibia lead levels. We conclude that genetic polymorphisms may modify uric acid mediation of lead-related adverse renal effects. SN - 0091-6765 UR - https://www.unboundmedicine.com/medline/citation/16263504/Associations_of_uric_acid_with_polymorphisms_in_the_delta_aminolevulinic_acid_dehydratase_vitamin_D_receptor_and_nitric_oxide_synthase_genes_in_Korean_lead_workers_ L2 - https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.7927?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -