Details:

Alternative Title:
Environ Health Perspect
Publisher's site:
http://dx.doi.org/10.1289/ehp.7927
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.
Subjects:
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Adult Biological Markers Female Genotype Humans Lead Male Middle Aged Nitric Oxide Synthase Type III Occupational Exposure Polymorphism, Genetic Porphobilinogen Synthase Receptors, Calcitriol Tibia 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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