Associations of Uric Acid with Polymorphisms in the δ-Aminolevulinic Acid Dehydratase, Vitamin D Receptor, and Nitric Oxide Synthase Genes in Korean Lead Workers

Details

• Alternative Title:
  Environ Health Perspect
• Personal Author:
  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
• 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:
  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

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• 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 ; 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
• Place as Subject:
  Republic of Korea
• Volume:
  113
• Issue:
  11
• 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:
  [PDF - 146.46 KB ]