Associations of Blood Pressure and Hypertension with Lead Dose Measures and Polymorphisms in the Vitamin D Receptor and d-Aminolevulinic Acid Dehydratase Genes

Abstract

Evidence suggests that lead and selected genes known to modify the toxicokinetics of lead--namely, those for the vitamin D receptor (VDR) and delta-aminolevulinic acid dehydratase (ALAD)--may independently influence blood pressure and hypertension risk. We report the relations among ALAD and VDR genotypes, three lead dose measures, and blood pressure and hypertension status in 798 Korean lead workers and 135 controls without occupational exposure to lead. Lead dose was assessed by blood lead, tibia lead measured by X-ray fluorescence, and dimercaptosuccinic acid (DMSA)-chelatable lead. Among lead workers, 9.9% (n = 79) were heterozygous for the ALAD(2) allele, and there were no ALAD(2) homozygotes; 11.2% (n = 89) had at least one copy of the VDR B allele, and 0.5% (n = 4) had the BB genotype. In linear regression models to control for covariates, VDR genotype (BB and Bb vs. bb), blood lead, tibia lead, and DMSA-chelatable lead were all positive predictors of systolic blood pressure. On average, lead workers with the VDR B allele, mainly heterozygotes, had systolic blood pressures that were 2.7-3.7 mm Hg higher than did workers with the bb genotype. VDR genotype was also associated with diastolic blood pressure; on average, lead workers with the VDR B allele had diastolic blood pressures that were 1.9-2.5 mm Hg higher than did lead workers with the VDR bb genotype (p = 0.04). VDR genotype modified the relation of age with systolic blood pressure; compared to lead workers with the VDR bb genotype, workers with the VDR B allele had larger elevations in blood pressure with increasing age. Lead workers with the VDR B allele also had a higher prevalence of hypertension compared to lead workers with the bb genotype [adjusted odds ratio (95% confidence interval) = 2.1 (1.0, 4.4), p = 0.05]. None of the lead biomarkers was associated with diastolic blood pressure, and tibia lead was the only lead dose measure that was a significant predictor of hypertension status. In contrast to VDR, ALAD genotype was not associated with the blood pressure measures and did not modify associations of the lead dose measures with any of the blood pressure measures. To our knowledge, these are the first data to suggest that the common genetic polymorphism in the VDR is associated with blood pressure and hypertension risk. We speculate that the BsmI polymorphism may be in linkage disequilibrium with another functional variant at the VDR locus or with a nearby gene.

Blood Lead Below 0.48 μmol/L (10 μg/dL) and Mortality Among US Adults

“…Both blood lead, which reflects recent exposure, and bone lead, which reflects cumulative exposure, have been associated with blood pressure increases. [27][28][29] Thus, it is unclear whether the adverse health effects of lead observed here were associated with current or cumulative exposures. In addition, because of declining lead levels in the decades before lead ascertainment in the present analysis, it is unclear whether the observed increased risk in mortality was due to lead exposure at baseline or lead mobilization from the skeleton.…”

Predictors of plasma lead among lithographic print shop workers in Mexico City

“…Hu et al [1994] point out that an increase in patella lead levels of 37 mg/g observed in construction workers are associated with a decrease of 11 g/L in hemoglobin even when blood lead concentrations were low (8.3 mg/dL, mean). Accumulation in bone is also associated with hypertension [Hu et al, 1996;Korrick et al, 1999;Lee et al, 2001;Rothenberg et al, 2002;Glenn et al, 2003] and reduced weight at birth [González-Cossío et al, 1997]. Therefore, the contribution of bonestored lead is important.…”

Lead Nephropathy: Revisiting an Overlooked Cause of Kidney Disease

“…Chia et al 70 in a study of Vietnamese and Singaporean lead workers, showed that workers with the ALAD2 allele appeared more susceptible to the toxic effects of lead on renal function, especially at higher lead levels. Another study 71 among Koreans subjects did not find any association between ALAD genotype with blood pressure, but reported that subjects with the VDR B gene allele in hetero and homozygous combination had higher systolic and diastolic blood pressure as well as higher prevalence of hypertension. In spite of the above mentioned association of the varied genetic variability in lead toxicity, more research is needed to justify the assessment of these genetic polymorphisms in lead exposure screening and evaluation.…”