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.ImagesFigure 1

The Epidemiology of Lead Toxicity in Adults: Measuring Dose and Consideration of Other Methodologic Issues

“…First, although more difficult, this bias could be avoided in occupational studies that assembled complete cohorts and randomly selected workers for study, including those who left the workplace early or late in their careers. Of interest is that studies that have assembled cohorts of all workers ever employed in a given plant or industry have reported many significant findings not previously observed (Schwartz et al 2000, 2001, 2005; Stewart et al 1999). Second, longitudinal studies, in comparing subjects with themselves in changes in health status over time, are somewhat less susceptible to this kind of bias, whether occupational or environment.…”

Functional principal component model for high-dimensional brain imaging

“…The data were derived from an epidemiologic study of the central nervous system effects of organic and inorganic lead in former organolead manufacturing workers, described in detail elsewhere (Schwartz et al, 2000a,b; Stewart et al, 1999). Subject scans were from a GE 1.5 Tesla Signa scanner.…”

Adult Lead Exposure: Time for Change

“…We must also prevent the shorter latency health effects of recent dose, as reflected in blood lead levels, such as elevations in blood pressure and the cognitive dysfunction present at only moderate blood lead levels. We must acknowledge that there are likely to be susceptible subgroups, as suggested by recent studies demonstrating worse lead-associated outcomes in persons with certain polymorphisms in the apolipoprotein E (Stewart et al 2001), vitamin D receptor (Lee et al 2001a, 2001b; Schwartz et al 2000a, 2000b), Na + ,K + -ATPase (Glenn et al 2001), and δ-aminolevulinic acid genes (Bergdahl et al 1997; Schwartz et al 2000a, 1997; Wetmur 1994; Wetmur et al 1991; Wu et al 2003), protein kinase C phenotypes (Hwang et al 2002), and persons with other common chronic diseases such as type II diabetes (Tsaih et al 2004), and promulgate lead standards that prevent adverse health outcomes in these most susceptible subgroups.…”