Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase genes

Evidence suggests that lead and selected genes known to modify the toxicoki netics of lead-namely, those for the vitamin D receptor (VDR) and delta -am inolevulinic acid dehydratase (ALAD)-may independently influence blood pres sure and hypertension risk. We report the relations among ALAD and VDR geno types, 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 le ad workers, 9.9% (n = 79) were heterozygous For the ALAD(2) allele, and the re 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 m odels to control for covariates, VDR genotype (BB and Bb vs. bb), blood lea d, tibia lead, and DMSA-chelatable lead were all positive predictors of sys tolic blood pressure. On average, lead workers with the VDR B allele, mainl y heterozygotes, had systolic blood pressures that were 2.7-3.7 mm Hg highe r than did workers with the bb genotype. VDR genotype was also associated w ith diastolic blood pressure; on average, lead workers with the VDR B allel e had diastolic blood pressures that were 1.9-2.5 mm Hg higher than did lea d workers with the VDR bb genotype (p = 0.04). VDR genotype modified the re lation of age with systolic blood pressure; compared to lead workers with t he VDR bb genotype, workers with die VDR B allele had larger elevations in blood pressure with increasing age. Lad workers with the VDR B allele also had a higher prevalence of hypertension compared to lead workers with the b b 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 signifi cant predictor of hypertension status. In contrast to VDR, ALAD genotype wa s not associated with the blood pressure measures and did not modify associ ations of the lead dose measures with any of the blood pressure measures. T o our knowledge, these are the first data to suggest that the common geneti c polymorphism in the VDR is associated with blood pressure and hypertensio n risk. We speculate that the BsmI polymorphism may be in linkage disequili brium with another functional variant at the VDR locus or with a nearby gen e.