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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.

Authors
Weaver-VM; Lee-BK; Todd-AC; Ahn-KD; Shi-W; Jaar-BG; Kelsey-KT; Lustberg-ME; Silbergeld-EK; Parsons-PJ; Wen-J; Schwartz-BS
Source
Environ Res 2006 Sep; 102(1):61-69
NIOSHTIC No.
20037679
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.
Keywords
Lead-poisoning; Lead-compounds; Kidneys; Kidney-damage; Humans; Men; Women; Age-groups; Epidemiology; Occupational-exposure; Metabolism; Author Keywords: d-aminolevulinic acid dehydratase; Endothelial nitric oxide synthase; Renal function; Lead exposure; Patella lead; Tibia lead; Vitamin D receptor
Contact
Virginia M. Weaver, Division of Occupational and Environmental Health, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Room 7041, Baltimore, MD, 21205
CODEN
ENVRAL
CAS No.
7439-92-1
Publication Date
20060901
Document Type
Journal Article
Email Address
vweaver@jhsph.edu
Funding Type
Grant
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T42-OH-008428
Issue of Publication
1
ISSN
0013-9351
Source Name
Environmental Research
State
MA; MD; NY
Performing Organization
Johns Hopkins University
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