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Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers.
Environ Res 2006; 102(1):61-9ER

Abstract

Genetic polymorphisms that affect lead toxicokinetics or toxicodynamics may be important modifiers of risk for adverse outcomes in lead-exposed populations. We recently reported associations between higher patella lead, which is hypothesized to represent a lead pool that is both bioavailable and cumulative, and adverse renal outcomes in current and former Korean lead workers. In the present study, we assessed effect modification by polymorphisms in the genes encoding for delta-aminolevulinic acid dehydratase (ALAD), the vitamin D receptor (VDR), and endothelial nitric oxide synthase on those associations. Similar analyses were conducted with three other lead biomarkers. Renal function was assessed via blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, urinary N-acetyl-beta-D-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) microg/dl, 75.1 (101.1)and 33.6 (43.4) microg Pb/g bone mineral, and 0.63 (0.75) microg Pb/mg creatinine, respectively, in 647 lead workers. Little evidence of effect modification by genotype on associations between patella lead and renal outcomes was observed. The VDR polymorphism did modify associations between the other lead biomarkers and the serum creatinine and calculated creatinine clearance. Higher lead dose was associated with worse renal function in participants with the variant B allele. Models in two groups, dichotomized by median age, showed that this effect was present in the younger half of the population. Limited evidence of effect modification by ALAD genotype was observed; higher blood lead levels were associated with higher calculated creatinine clearance among participants with the ALAD(1-2) genotype. In conclusion, VDR and/or ALAD genotypes modified associations between all the lead biomarkers, except patella lead, and the renal outcomes.

Authors+Show Affiliations

Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA. vweaver@jhsph.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16487505

Citation

Weaver, Virginia M., et al. "Effect Modification By Delta-aminolevulinic Acid Dehydratase, Vitamin D Receptor, and Nitric Oxide Synthase Gene Polymorphisms On Associations Between Patella Lead and Renal Function in Lead Workers." Environmental Research, vol. 102, no. 1, 2006, pp. 61-9.
Weaver VM, Lee BK, Todd AC, et al. Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers. Environ Res. 2006;102(1):61-9.
Weaver, V. M., Lee, B. K., Todd, A. C., Ahn, K. D., Shi, W., Jaar, B. G., ... Schwartz, B. S. (2006). Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers. Environmental Research, 102(1), pp. 61-9.
Weaver VM, et al. Effect Modification By Delta-aminolevulinic Acid Dehydratase, Vitamin D Receptor, and Nitric Oxide Synthase Gene Polymorphisms On Associations Between Patella Lead and Renal Function in Lead Workers. Environ Res. 2006;102(1):61-9. PubMed PMID: 16487505.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect modification by delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase gene polymorphisms on associations between patella lead and renal function in lead workers. AU - Weaver,Virginia M, AU - Lee,Byung-Kook, AU - Todd,Andrew C, AU - Ahn,Kyu-Dong, AU - Shi,Weiping, AU - Jaar,Bernard G, AU - Kelsey,Karl T, AU - Lustberg,Mark E, AU - Silbergeld,Ellen K, AU - Parsons,Patrick J, AU - Wen,Jiayu, AU - Schwartz,Brian S, Y1 - 2006/02/17/ PY - 2005/08/15/received PY - 2005/12/19/revised PY - 2006/01/04/accepted PY - 2006/2/21/pubmed PY - 2006/10/18/medline PY - 2006/2/21/entrez SP - 61 EP - 9 JF - Environmental research JO - Environ. Res. VL - 102 IS - 1 N2 - Genetic polymorphisms that affect lead toxicokinetics or toxicodynamics may be important modifiers of risk for adverse outcomes in lead-exposed populations. We recently reported associations between higher patella lead, which is hypothesized to represent a lead pool that is both bioavailable and cumulative, and adverse renal outcomes in current and former Korean lead workers. In the present study, we assessed effect modification by polymorphisms in the genes encoding for delta-aminolevulinic acid dehydratase (ALAD), the vitamin D receptor (VDR), and endothelial nitric oxide synthase on those associations. Similar analyses were conducted with three other lead biomarkers. Renal function was assessed via blood urea nitrogen, serum creatinine, measured and calculated creatinine clearances, urinary N-acetyl-beta-D-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) microg/dl, 75.1 (101.1)and 33.6 (43.4) microg Pb/g bone mineral, and 0.63 (0.75) microg Pb/mg creatinine, respectively, in 647 lead workers. Little evidence of effect modification by genotype on associations between patella lead and renal outcomes was observed. The VDR polymorphism did modify associations between the other lead biomarkers and the serum creatinine and calculated creatinine clearance. Higher lead dose was associated with worse renal function in participants with the variant B allele. Models in two groups, dichotomized by median age, showed that this effect was present in the younger half of the population. Limited evidence of effect modification by ALAD genotype was observed; higher blood lead levels were associated with higher calculated creatinine clearance among participants with the ALAD(1-2) genotype. In conclusion, VDR and/or ALAD genotypes modified associations between all the lead biomarkers, except patella lead, and the renal outcomes. SN - 0013-9351 UR - https://www.unboundmedicine.com/medline/citation/16487505/Effect_modification_by_delta_aminolevulinic_acid_dehydratase_vitamin_D_receptor_and_nitric_oxide_synthase_gene_polymorphisms_on_associations_between_patella_lead_and_renal_function_in_lead_workers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0013-9351(06)00002-8 DB - PRIME DP - Unbound Medicine ER -