Details:

Alternative Title:
Environ Health Perspect
Publisher's site:
http://dx.doi.org/
Personal Author:
Weaver, Virginia M. ; Schwartz, Brian S. ; Jaar, Bernard G. ; Ahn, Kyu-Dong ; Todd, Andrew C. ; ... More +
Weaver, Virginia M. ; Schwartz, Brian S. ; Jaar, Bernard G. ; Ahn, Kyu-Dong ; Todd, Andrew C. ; Lee, Sung-Soo ; Kelsey, Karl T. ; Silbergeld, Ellen K. ; Lustberg, Mark E. ; Parsons, Patrick J. ; Wen, Jiayu ; Lee, Byung-Kook Less -
Description:
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.
Subject:
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Adult Biological Markers Endothelial Nitric Oxide Synthase Female Genetic Susceptibility Factors Genotype Humans Kidney Function Lead Lead Exposure Male Middle Aged Nitric Oxide Synthase Type III Occupational Exposure Polymorphism, Genetic Porphobilinogen Synthase Receptors, Calcitriol Research Tibia Uric Acid Vitamin D Receptor δ-aminolevulinic Acid Dehydratase Uric Acid
Source:
Environ Health Perspect. 2005; 113(11):1509-1515.
Document Type:
Journal Article
Funding:
2 ES07198/ES/NIEHS NIH HHS/United States ; ES00002/ES/NIEHS NIH HHS/United States ; ES07198/ES/NIEHS NIH HHS/United States ; F30-ES05922-02/ES/NIEHS NIH HHS/United States ; R01 ES007198-05/ES/NIEHS NIH HHS/United States ; ... More +
2 ES07198/ES/NIEHS NIH HHS/United States ; ES00002/ES/NIEHS NIH HHS/United States ; ES07198/ES/NIEHS NIH HHS/United States ; F30-ES05922-02/ES/NIEHS NIH HHS/United States ; R01 ES007198-05/ES/NIEHS NIH HHS/United States ; R01 ES007198-06/ES/NIEHS NIH HHS/United States ; R01 ES007198-07/ES/NIEHS NIH HHS/United States ; R01 ES007198-08/ES/NIEHS NIH HHS/United States ; TS288-14/14/TS/ATSDR CDC HHS/United States Less -
Place as Subject:
Republic of Korea
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:355e6a5bb708790b8668bcad49e996fff5d39739f0e73c80657809f613222b6f
Download URL:
https://stacks.cdc.gov/view/cdc/31156/cdc_31156_DS1.pdf
File Type:

Supporting Files

• 	license.txt	txt
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