Associations of uric acid with polymorphisms in the δ-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers

Virginia M. Weaver, Brian S. Schwartz, Bernard G. Jaar, Kyu Dong Ahn, Andrew C. Todd, Sung Soo Lee, Karl T. Kelsey, Ellen K. Silbergeld, Mark E. Lustberg, Patrick J. Parsons, Jiayu Wen, Byung Kook Lee

Research output: Contribution to journalArticlepeer-review

Abstract

Recent research suggests that uric acid pray 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: δ-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 μg/g bone mineral, 32.0± 15.0 g/dL, and 0.77± 0.86 μg/mg creatinine, respectively, in 798 current and former lead workers. Participants with the eNOS Asp allele had lower mean serum uric acid compared with those with the Glu/Glu genotype. Among older workers (age ≥ 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 VDR B 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.

Original languageEnglish (US)
Pages (from-to)1509-1515
Number of pages7
JournalEnvironmental health perspectives
Volume113
Issue number11
DOIs
StatePublished - Nov 2005

Keywords

  • Endothelial nitric oxide synthase
  • Genetic susceptibility factors
  • Kidney function
  • Lead exposure
  • Uric acid
  • Vitamin D receptor
  • δ-aminolevulinic acid dehydratase

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Associations of uric acid with polymorphisms in the δ-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers'. Together they form a unique fingerprint.

Cite this