Associations of tibial lead levels with BsmI polymorphisms in the vitamin D receptor in former organolead manufacturing workers

We evaluated associations of tibial lead levels with polymorphisms in the v itamin D receptor (VDR) in 504 former organolead manufacturing workers with past exposure to lead. In this cross-sectional study, we measured tibial l ead by Cd-109 K-shell X-ray fluorescence. Tibial lead was evaluated in subj ects 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 heterozygo us (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 mu g 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 mod ified the relation between age and tibial lead concentrations; subjects wit h the B allele had larger increases in tibia lead concentrations with incre asing age (0.37, 0.48, and 0.67 mu g/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 expo sure to lead and tibial lead concentrations. Subjects with bb evidenced an average decline in tibial lead concentrations of 0.10 mu g/g per year since their last exposure to lead, whereas subjects with Bb and BB evidenced ave rage increases of 0.03 and 0.11 mu g/g per year, respectively (the adjusted p-value for trend in slopes = 0.01). Polymorphisms in the vitamin D recept or modified the relations of age and years since the last exposure to lead with tibial lead concentrations. Although controversy remains on the influe nce of the VDR genotype on bone mineral density, the data suggest that vari ant VDR alleles modify lead concentrations in bone, either by influencing l ead content or calcium content or both.