TY - JOUR
T1 - Effect modification by δ-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.
N1 - Funding Information:
We thank Drs. Yong-Bae Kim, Bong-Ki Jang, Gap-Soo Lee, and Sung-Soo Lee for assistance in data collection in South Korea and Professor James Wetmur of The Mount Sinai School of Medicine for providing the nested primers for ALAD genotyping. This research was supported by NIEHS Grants ES07198 (Dr. Schwartz), 2 ES07198 (Dr. Weaver), and ES00002 (Dr. Kelsey), National Research Service Award F30-ES05922-02 (Dr. Lustberg), Korea Research Foundation Grant KRF-2000-00545 (Dr. Lee), and Centers for Disease Control and Prevention Grant ATPM TS288-14/14 (Drs. Lustberg and Silbergeld).
PY - 2006/9
Y1 - 2006/9
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 δ-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-β-d-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) μg/dl, 75.1 (101.1) and 33.6 (43.4) μg Pb/g bone mineral, and 0.63 (0.75) μg 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.
AB - 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 δ-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-β-d-glucosaminidase, and retinol-binding protein. Mean (SD) blood, patella, tibia, and dimercaptosuccinic acid-chelatable lead values were 30.9 (16.7) μg/dl, 75.1 (101.1) and 33.6 (43.4) μg Pb/g bone mineral, and 0.63 (0.75) μg 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.
KW - Endothelial nitric oxide synthase
KW - Lead exposure
KW - Patella lead
KW - Renal function
KW - Tibia lead
KW - Vitamin D receptor
KW - δ-aminolevulinic acid dehydratase
UR - http://www.scopus.com/inward/record.url?scp=33746070801&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2006.01.001
DO - 10.1016/j.envres.2006.01.001
M3 - Article
C2 - 16487505
AN - SCOPUS:33746070801
SN - 0013-9351
VL - 102
SP - 61
EP - 69
JO - Environmental Research
JF - Environmental Research
IS - 1
ER -