title: Associations of tibial lead levels with BsmI polymorphisms in the vitamin D receptor in former organolead manufacturing workers.
abstract: We evaluated associations of tibial lead levels with polymorphisms in the vitamin D receptor (VDR) in 504 former organolead manufacturing workers with past exposure to lead. In this cross-sectional study, we measured tibial lead by (109)Cd K-shell X-ray fluorescence. Tibial lead was evaluated in subjects with different VDR genotypes defined using the BsmI restriction enzyme, adjusting for confounding variables. Study participants had a mean age +/- SD of 57.4 +/- 7.6 years. A total of 169 (33.5%) subjects were homozygous for the BsmI restriction site (designated bb), 251 (49.8%) were heterozygous (Bb), and 84 (16.7%) were homozygous for the absence of the restriction site (BB). Among all of the study subjects, tibial lead concentrations were low, with a mean +/- SD of 14.4 +/- 9.3 microg Pb/g bone mineral. There were only small differences in tibial lead concentrations by VDR genotype, with mean +/- SD tibial lead concentrations of 13.9 +/- 7.9, 14.3 +/- 9.5, and 15.5 +/- 11.1 in subjects with bb, Bb, and BB, respectively. In a multiple linear regression model of tibial lead concentrations, the VDR genotype modified the relation between age and tibial lead concentrations; subjects with the B allele had larger increases in tibial lead concentrations with increasing age (0.37, 0.48, and 0.67 microg/g per year of age in subjects with bb, Bb, and BB, respectively; the adjusted p-value for trend in slopes = 0.04). The VDR genotype also modified the relation between years since last exposure to lead and tibial lead concentrations. Subjects with bb evidenced an average decline in tibial lead concentrations of 0.10 microg/g per year since their last exposure to lead, whereas subjects with Bb and BB evidenced average increases of 0.03 and 0.11 microg/g per year, respectively (the adjusted p-value for trend in slopes = 0.01). Polymorphisms in the vitamin D receptor modified the relations of age and years since the last exposure to lead with tibial lead concentrations. Although controversy remains on the influence of the VDR genotype on bone mineral density, the data suggest that variant VDR alleles modify lead concentrations in bone, either by influencing lead content or calcium content or both.
authors.affiliation: Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland 21205, USA. bschwart@jhsph.edu
authors.forename: B S
authors.initials: BS
authors.lastname: Schwartz
authors.forename: W F
authors.initials: WF
authors.lastname: Stewart
authors.forename: K T
authors.initials: KT
authors.lastname: Kelsey
authors.forename: D
authors.initials: D
authors.lastname: Simon
authors.forename: S
authors.initials: S
authors.lastname: Park
authors.forename: J M
authors.initials: JM
authors.lastname: Links
authors.forename: A C
authors.initials: AC
authors.lastname: Todd
mesh_terms: D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D001822:Body Burden; D015519:Bone Density; D015986:Confounding Factors, Epidemiologic; D003430:Cross-Sectional Studies; D004784:Environmental Monitoring / Q000379:methods*; D005838:Genotype; D006801:Humans; D007854:Lead / Q000032:analysis*; D016014:Linear Models; D008669:Metallurgy; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis*; D012150:Polymorphism, Restriction Fragment Length; D011859:Radiography; D018167:Receptors, Calcitriol / Q000235:genetics*; D015183:Restriction Mapping; D013052:Spectrometry, X-Ray Emission; D013977:Tibia / Q000737:chemistry* / Q000000981:diagnostic imaging*; D013997:Time Factors; D014481:United States
chemical_list: D018167:Receptors, Calcitriol; D007854:Lead