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Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase genes.
Environ Health Perspect. 2001 Apr; 109(4):383-9.EH

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.

Authors+Show Affiliations

Institute of Industrial Medicine, Soonchunhyang University, Chonan, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11335187

Citation

Lee, B K., et al. "Associations of Blood Pressure and Hypertension With Lead Dose Measures and Polymorphisms in the Vitamin D Receptor and Delta-aminolevulinic Acid Dehydratase Genes." Environmental Health Perspectives, vol. 109, no. 4, 2001, pp. 383-9.
Lee BK, Lee GS, Stewart WF, et al. Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase genes. Environ Health Perspect. 2001;109(4):383-9.
Lee, B. K., Lee, G. S., Stewart, W. F., Ahn, K. D., Simon, D., Kelsey, K. T., Todd, A. C., & Schwartz, B. S. (2001). Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase genes. Environmental Health Perspectives, 109(4), 383-9.
Lee BK, et al. Associations of Blood Pressure and Hypertension With Lead Dose Measures and Polymorphisms in the Vitamin D Receptor and Delta-aminolevulinic Acid Dehydratase Genes. Environ Health Perspect. 2001;109(4):383-9. PubMed PMID: 11335187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Associations of blood pressure and hypertension with lead dose measures and polymorphisms in the vitamin D receptor and delta-aminolevulinic acid dehydratase genes. AU - Lee,B K, AU - Lee,G S, AU - Stewart,W F, AU - Ahn,K D, AU - Simon,D, AU - Kelsey,K T, AU - Todd,A C, AU - Schwartz,B S, PY - 2001/5/4/pubmed PY - 2002/1/24/medline PY - 2001/5/4/entrez SP - 383 EP - 9 JF - Environmental health perspectives JO - Environ. Health Perspect. VL - 109 IS - 4 N2 - 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. SN - 0091-6765 UR - https://www.unboundmedicine.com/medline/citation/11335187/Associations_of_blood_pressure_and_hypertension_with_lead_dose_measures_and_polymorphisms_in_the_vitamin_D_receptor_and_delta_aminolevulinic_acid_dehydratase_genes_ L2 - https://ehp.niehs.nih.gov/doi/full/10.1289/ehp.01109383?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -