Gap Soo Lee

Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes.

A cross-sectional study was performed to evaluate the influence of polymorphisms in the [delta]-aminolevulinic acid dehydratase (ALAD) and vitamin D receptor (VDR) genes on blood lead, tibia lead, and dimercaptosuccinic acid (DMSA)-chelatable lead levels in 798 lead workers and 135 controls without occupational lead exposure in the Republic of Korea. Tibia lead was assessed with a 30-min measurement by (109)Cd-induced K-shell X-ray fluorescence, and DMSA-chelatable lead was estimated as 4-hr urinary lead excretion after oral administration of 10 mg/kg DMSA. The primary goals of the analysis were to examine blood lead, tibia lead, and DMSA-chelatable lead levels by ALAD and VDR genotypes, controlling for covariates; and to evaluate whether ALAD and VDR genotype modified relations among the different lead biomarkers. There was a wide range of blood lead (4-86 microg/dL), tibia lead (-7-338 microg Pb/g bone mineral), and DMSA-chelatable lead (4.8-2,103 microg) levels among lead workers. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele and there were no homozygotes. For VDR, 10.7% (n = 85) had the Bb genotype, and 0.5% (n = 4) had the BB genotype. Although the ALAD and VDR genes are located on different chromosomes, lead workers homozygous for the ALAD(1) allele were much less likely to have the VDR bb genotype (crude odds ratio = 0.29, 95% exact confidence interval = 0.06-0.91). In adjusted analyses, subjects with the ALAD(2) allele had higher blood lead levels (on average, 2.9 microg/dL, p = 0.07) but no difference in tibia lead levels compared with subjects without the allele. In adjusted analyses, lead workers with the VDR B allele had significantly (p < 0.05) higher blood lead levels (on average, 4.2 microg/dL), chelatable lead levels (on average, 37.3 microg), and tibia lead levels (on average, 6.4 microg/g) than did workers with the VDR bb genotype. The current data confirm past observations that the ALAD gene modifies the toxicokinetics of lead and also provides new evidence that the VDR gene does so as well.

Associations of lead biomarkers with renal function in Korean lead workers

Aims: To compare associations of lead biomarkers with renal function in current and former lead workers. Methods: Cross sectional analysis of first year results from a longitudinal study of 803 lead workers and 135 controls in South Korea. Clinical renal function was assessed by blood urea nitrogen (BUN), serum creatinine, and measured and calculated creatinine clearance. Urinary N-acetyl-β-D-glucosaminidase (NAG) and retinol-binding protein were also measured. Results: Mean (SD) tibia lead, blood lead, and DMSA chelatable lead levels in lead workers were 37.2 (40.4) μg/g bone mineral, 32.0 (15.0) μg/dl, and 767.8 (862.1) μg/g creatinine, respectively. Higher lead measures were associated with worse renal function in 16/42 models. When influential outliers were removed, higher lead measures remained associated with worse renal function in nine models. An additional five associations were in the opposite direction. Effect modification by age was observed. In 3/16 models, associations between higher lead measures and worse clinical renal function in participants in the oldest age tertile were significantly different from associations in those in the youngest age tertile which were in the opposite direction. Mean urinary cadmium (CdU) was 1.1 μg/g creatinine (n = 191). Higher CdU levels were associated with higher NAG. Conclusions: These data suggest that lead has an adverse effect on renal function in the moderate dose range, particularly in older workers. Associations between higher lead measures and lower BUN and serum creatinine and higher creatinine clearances may represent lead induced hyperfiltration. Environmental cadmium may also have an adverse renal impact, at least on NAG.

Predictors of DMSA chelatable lead, tibial lead, and blood lead in 802 Korean lead workers

OBJECTIVES To examine the interrelations among chelatable lead (by dimercaptosuccinic acid, DMSA), tibial lead, and blood lead concentrations in 802 Korean workers with occupational exposure to lead and 135 employed controls with only environmental exposure to lead. METHODS This was a cross sectional study wherein tibial lead, DMSA chelatable lead, and blood lead were measured. Linear regression was used to identify predictors of the three lead biomarkers, evaluating the influence of age, job duration, sex, education level, alcohol and tobacco use, creatinine clearance rate, and body mass index. RESULTS DMSA chelatable lead concentrations ranged from 4.8 to 2102.9 μg and were positively associated with age, current smoking, and creatinine clearance rate. On average, women had 64 μg less DMSA chelatable lead than men. When blood lead and its square were added to a model with age, sex, current smoking, body mass index, and creatinine clearance rate, blood lead accounted for the largest proportion of the variance and sex became of borderline significance. Tibial lead concentrations ranged from −7 to 338 μg/g bone mineral and were positively associated with age, job duration, and body mass index. Women had, on average, 9.7 μg/g less tibial lead than men. Blood lead concentrations ranged from 4.3 to 85.7 μg/dl and were positively associated with age and tibial lead, whereas current smokers had higher blood lead concentrations and women had lower blood lead concentrations. CONCLUSIONS The data suggest that age and sex are both predictors of DMSA chelatable lead, blood lead, and tibial lead concentrations and that tibial lead stores in older subjects are less bioavailable and may contribute less to blood lead concentrations than tibial lead stores in younger subjects. Although blood lead concentrations accounted for a large proportion of the variance in DMSA chelatable lead concentrations, suggesting that measurement of both in epidemiological studies may not be necessary, the efficacy of each measure in predicting health outcomes in epidemiological studies awaits further investigation.

Comparison of Patella Lead With Blood Lead and Tibia Lead and Their Associations With Neurobehavioral Test Scores

Objective: Lead exposure in adults is associated with worse cognitive function in cross-sectional and longitudinal studies. Previous studies have mainly examined relations with blood lead or cortical bone lead; few have examined trabecular bone lead. Methods: We performed a cross-sectional analysis of the relations of patella lead and other lead biomarkers with measures of neurobehavioral and peripheral nervous system function in 652 lead workers. Results: Patella lead was found to be associated with worse performance on seven of 19 tests of manual dexterity, sensory vibration threshold, and depressive symptoms. The associations of patella lead with cognitive function were essentially similar to those with blood lead or tibia lead but of somewhat lower magnitude. Conclusions: In this study, measurement of patella lead did not aid causal inference regarding cognitive effects when compared with blood lead and tibia lead.

Different Effects of Serum Iron Status on the Relationship between Blood Lead and Zinc Protoporphyrin in Lead Workers in Korea

Different Effects of Serum Iron Status on the Relationship between Blood Lead and Zinc Protoporphyrin in Lead Workers in Korea: Hyun‐Cheol Ahn, et al. Department of Preventive Medicine and Institute of Industrial Medicine, School of Medicine, Soonchunhyang University—This study was conducted to determine whether there was a different toxic effect of lead on heme synthesis by serum iron status in 360 lead workers in Korea. We examined the association between blood lead (PbB) and zinc protoporphyrin (ZPP) in whole blood according to the level of serum iron in low to moderate lead‐exposed workers in 1997‐1998. Serum iron levels (FeS) were divided into two groups: iron‐deficient group (serum iron < 80 μg/d/, 57 subjects) and iron‐sufficient group (serum iron ≥ 80 μg/d/, 303 subjects). Blood lead corrected by the standard value for hemoglobin (15 g/ d1) as an explanatory variable was assessed to explain the variance of ZPP. After adjusting for possible confounders, such as age, body mass index (BMI), cigarette smoking, alcohol drinking, and size of factory, the linear slope of corrected PbB on ZPP in the iron‐deficient group was statistically higher than that of the iron‐sufficient group. The interaction term between corrected PbB and ZPP with the modification of the serum iron status was statistically significant in the regression model (p=0.0053). The result suggests that the relationship between corrected PbB and ZPP may be modified by the serum iron status in male lead‐exposed workers.