Associations of renal function with polymorphisms in the delta-aminolevulinic acid dehydratase, vitamin D receptor, and nitric oxide synthase genes in Korean lead workers.

Abstract

We analyzed data from 798 lead workers to determine whether polymorphisms in the genes encoding delta-aminolevulinic acid dehydratase (ALAD), endothelial nitric oxide synthase (eNOS), and the vitamin D receptor (VDR) were associated with or modified relations of lead exposure and dose measures with renal outcomes. Lead exposure was assessed with job duration, blood lead, dimercaptosuccinic acid (DMSA)-chelatable lead, and tibia lead. Renal function was assessed with blood urea nitrogen (BUN), serum creatinine, measured creatinine clearance, calculated creatinine clearance and urinary N-acetyl-beta-D-glucosaminidase (NAG), and retinol-binding protein. Mean (+/- SD) tibia lead, blood lead, and DMSA-chelatable lead levels were 37.2 +/- 40.4 microg/g bone mineral, 32.0 +/- 15.0 microg/dL, and 767.8 +/- 862.1 microg/g creatinine, respectively. After adjustment, participants with the ALAD(2) allele had lower mean serum creatinine and higher calculated creatinine clearance. We observed effect modification by ALAD on associations between blood lead and/or DMSA-chelatable lead and three renal outcomes. Among those with the ALAD(1-2) genotype, higher lead measures were associated with lower BUN and serum creatinine and higher calculated creatinine clearance. Participants with the eNOS variant allele were found to have higher measured creatinine clearance and BUN. In participants with the Asp allele, longer duration working with lead was associated with higher serum creatinine and lower calculated creatinine clearance and NAG; all were significantly different from relations in those with the Glu/Glu genotype except NAG (p = 0.08). No significant differences were seen in renal outcomes by VDR genotype, nor was consistent effect modification observed. The ALAD findings could be explained by lead-induced hyperfiltration.

Investigation of delta-aminolevulinic acid dehydratase polymorphism affecting hematopoietic, hepatic and renal toxicity from lead in Han subjects of southwestern China

“…Chia et al (4) proposed that workers with the ALAD2 allele appeared more susceptible to the effects of lead on renal function especially at higher levels. Weaver et al (23,24,25) reported that higher blood lead level was associated with worse renal function and higher blood lead level was associated with higher NAG and CCE among participants with the ALAD1-1 genotype.…”

Characterizing Golden Eagle Risk to Lead and Anticoagulant Rodenticide Exposure: A Review

“…As part of a longitudinal study of health outcomes among Korean lead workers, cross-sectional studies of potential associations between biomarkers of lead exposure (PbB, tibia lead, DMSA evoked urinary lead) have been conducted (Weaver et al 2003a(Weaver et al , 2003b(Weaver et al , 2005a(Weaver et al , 2005b. The cross-sectional study of the first of three longitudinal evaluations included 803 current and former lead workers (age range, 18-65 years; 639 males) and 135 controls (age range, 22-60 years; 124 males), enrolled in the study during the period 1997-1999 (Weaver et al 2003a(Weaver et al , 2005a.…”

Selected work-related nephropathies

“…U koreań-skich pracowników narażonych na Pb wykazano zwią-zek allelu ALAD2 z niższym poziomem mocznika i kreatyniny w surowicy oraz wyższym klirensem kreatyniny [36]. Obserwowane zmiany mogą być następstwem hiperfiltracji indukowanej przez Pb i zależnej od wariantu ALAD [36].…”