Associations of renal function 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, Kyu Dong Ahn, Walter F. Stewart, Karl T. Kelsey, Andrew C. Todd, Jiayu Wen, David J. Simon, Mark E. Lustberg, Patrick J. Parsons, Ellen K. Silbergeld, Byung Kook Lee

Research output: Contribution to journalReview articlepeer-review

Abstract

We analyzed data from 798 lead workers to determine whether polymorphisms in the genes encoding δ-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR) were associated with or modified relations of lead exposure and dose measures with renal outcomes. Lead exposure was assessed with job duration, blood lead, dimercaptosuccinic acid (DMSA)-chelatable lead, and tibia lead. Renal function was assessed with blood urea nitrogen (BUN), serum creatinine, measured creatinine clearance, calculated creatinine clearance and urinary N-acetyl-β-D-glucosaminidase (NAG), and retinol-binding protein. Mean (± SD) tibia lead, blood lead, and DMSA-chelatable lead levels were 37.2 ± 40.4 μg/g bone mineral, 32.0 ± 15.0 μg/dL, and 767.8 ± 862.1 μg/g creatinine, respectively. After adjustment, participants with the ALAD2 allele had lower mean serum creatinine and higher calculated creatinine clearance. We observed effect modification by ALAD on associations between blood lead and/or DMSA-chelatable lead and three renal outcomes. Among those with the ALAD1-2 genotype, higher lead measures were associated with lower BUN and serum creatinine and higher calculated creatinine clearance. Participants with the eNOS variant allele were found to have higher measured creatinine clearance and BUN. In participants with the Asp allele, longer duration working with lead was associated with higher serum creatinine and lower calculated creatinine clearance and NAG; all were significantly different from relations in those with the Glu/Glu genotype except NAG (p = 0.08). No significant differences were seen in renal outcomes by VDR genotype, nor was consistent effect modification observed. The ALAD findings could be explained by lead-induced hyperfiltration.

Original languageEnglish (US)
Pages (from-to)1613-1619
Number of pages7
JournalEnvironmental health perspectives
Volume111
Issue number13
DOIs
StatePublished - Oct 1 2003

Keywords

  • Endothelial nitric oxide synthase
  • Genetic susceptibility factors
  • Lead exposure
  • N-acetyl-β-D-glucosaminidase (NAG)
  • Renal function
  • Retinol-binding protein
  • Vitamin D receptor
  • δ-aminolevulinic acid dehydratase

ASJC Scopus subject areas

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

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