| Autor: |
Weaver, Virginia M.1,2, Schwartz, Brian S.1,2,3, Jaar, Bernard G.2,3, Kyu-Dong Ahn4, Todd, Andrew C.5, Sung-Soo Lee4, Kelsey, Karl T.6, Silbergeld, Ellen K.7, Lustberg, Mark E.8, Parsons, Patrick J.9, Jiayu Wen1, Byung-Kook Lee4 leebkk@asan.sch.kr |
| Předmět: |
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| Zdroj: |
Environmental Health Perspectives. Nov2005, Vol. 113 Issue 11, p1509. 7p. 5 Charts, 3 Graphs. |
| Abstrakt: |
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: -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 eNOSAsp 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 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
GreenFILE |
| Externí odkaz: |
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