title: Associations of uric acid with polymorphisms in the delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers.
abstract: 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.
authors.affiliation: Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA.
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Weaver
authors.forename: Brian S
authors.initials: BS
authors.lastname: Schwartz
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Jaar
authors.forename: Kyu-Dong
authors.initials: KD
authors.lastname: Ahn
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Todd
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Lee
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Silbergeld
authors.forename: Mark E
authors.initials: ME
authors.lastname: Lustberg
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Parsons
authors.forename: Jiayu
authors.initials: J
authors.lastname: Wen
authors.forename: Byung-Kook
authors.initials: BK
authors.lastname: Lee
mesh_terms: D000328:Adult; D015415:Biomarkers; D005260:Female; D005838:Genotype; D006801:Humans; D007723:Korea; D007854:Lead / Q000032:analysis / Q000097:blood / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D000623:Porphobilinogen Synthase / Q000235:genetics*; D018167:Receptors, Calcitriol / Q000235:genetics*; D013977:Tibia / Q000737:chemistry; D014527:Uric Acid / Q000097:blood*
chemical_list: D015415:Biomarkers; D018167:Receptors, Calcitriol; D014527:Uric Acid; D007854:Lead; D052250:Nitric Oxide Synthase Type III; D000623:Porphobilinogen Synthase