Search tips
Search criteria 


Logo of envhperEnvironmental Health PerspectivesBrowse ArticlesAbout EHPGeneral InformationAuthorsMediaProgramsPartnerships
Environ Health Perspect. 2000 March; 108(3): 199–203.
PMCID: PMC1637981
Research Article

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 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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Fullmer CS. Intestinal lead and calcium absorption: effect of 1,25-dihydroxycholecalciferol and lead status. Proc Soc Exp Biol Med. 1990 Jul;194(3):258–264. [PubMed]
  • Fullmer CS. Intestinal interactions of lead and calcium. Neurotoxicology. 1992 Winter;13(4):799–807. [PubMed]
  • Mahaffey KR, Gartside PS, Glueck CJ. Blood lead levels and dietary calcium intake in 1- to 11-year-old children: the Second National Health and Nutrition Examination Survey, 1976 to 1980. Pediatrics. 1986 Aug;78(2):257–262. [PubMed]
  • Bogden JD, Kemp FW, Han S, Murphy M, Fraiman M, Czerniach D, Flynn CJ, Banua ML, Scimone A, Castrovilly L, et al. Dietary calcium and lead interact to modify maternal blood pressure, erythropoiesis, and fetal and neonatal growth in rats during pregnancy and lactation. J Nutr. 1995 Apr;125(4):990–1002. [PubMed]
  • Gulson BL, Mahaffey KR, Jameson CW, Mizon KJ, Korsch MJ, Cameron MA, Eisman JA. Mobilization of lead from the skeleton during the postnatal period is larger than during pregnancy. J Lab Clin Med. 1998 Apr;131(4):324–329. [PubMed]
  • Hu H, Milder FL, Burger DE. X-ray fluorescence: issues surrounding the application of a new tool for measuring burden of lead. Environ Res. 1989 Aug;49(2):295–317. [PubMed]
  • Todd AC, Chettle DR. In vivo X-ray fluorescence of lead in bone: review and current issues. Environ Health Perspect. 1994 Feb;102(2):172–177. [PMC free article] [PubMed]
  • Kristal-Boneh E, Froom P, Yerushalmi N, Harari G, Ribak J. Calcitropic hormones and occupational lead exposure. Am J Epidemiol. 1998 Mar 1;147(5):458–463. [PubMed]
  • Smith CM, DeLuca HF, Tanaka Y, Mahaffey KR. Effect of lead ingestion on functions of vitamin D and its metabolites. J Nutr. 1981 Aug;111(8):1321–1329. [PubMed]
  • Morrison NA, Yeoman R, Kelly PJ, Eisman JA. Contribution of trans-acting factor alleles to normal physiological variability: vitamin D receptor gene polymorphism and circulating osteocalcin. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6665–6669. [PubMed]
  • Barger-Lux MJ, Heaney RP, Hayes J, DeLuca HF, Johnson ML, Gong G. Vitamin D receptor gene polymorphism, bone mass, body size, and vitamin D receptor density. Calcif Tissue Int. 1995 Aug;57(2):161–162. [PubMed]
  • Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA. Prediction of bone density from vitamin D receptor alleles. Nature. 1994 Jan 20;367(6460):284–287. [PubMed]
  • Cooper GS, Umbach DM. Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis. J Bone Miner Res. 1996 Dec;11(12):1841–1849. [PubMed]
  • Sainz J, Van Tornout JM, Loro ML, Sayre J, Roe TF, Gilsanz V. Vitamin D-receptor gene polymorphisms and bone density in prepubertal American girls of Mexican descent. N Engl J Med. 1997 Jul 10;337(2):77–82. [PubMed]
  • Viitanen A, Kärkkäinen M, Laitinen K, Lamberg-Allardt C, Kainulainen K, Räsänen L, Viikari J, Välimäki MJ, Kontula K. Common polymorphism of the vitamin D receptor gene is associated with variation of peak bone mass in young finns. Calcif Tissue Int. 1996 Oct;59(4):231–234. [PubMed]
  • Fleet JC, Harris SS, Wood RJ, Dawson-Hughes B. The BsmI vitamin D receptor restriction fragment length polymorphism (BB) predicts low bone density in premenopausal black and white women. J Bone Miner Res. 1995 Jun;10(6):985–990. [PubMed]
  • Melhus H, Kindmark A, Amér S, Wilén B, Lindh E, Ljunghall S. Vitamin D receptor genotypes in osteoporosis. Lancet. 1994 Oct 1;344(8927):949–950. [PubMed]
  • Francis RM, Harrington F, Turner E, Papiha SS, Datta HK. Vitamin D receptor gene polymorphism in men and its effect on bone density and calcium absorption. Clin Endocrinol (Oxf) 1997 Jan;46(1):83–86. [PubMed]
  • Tsai KS, Hsu SH, Cheng WC, Chen CK, Chieng PU, Pan WH. Bone mineral density and bone markers in relation to vitamin D receptor gene polymorphisms in Chinese men and women. Bone. 1996 Nov;19(5):513–518. [PubMed]
  • Spotila LD, Caminis J, Johnston R, Shimoya KS, O'Connor MP, Prockop DJ, Tenenhouse A, Tenenhouse HS. Vitamin D receptor genotype is not associated with bone mineral density in three ethnic/regional groups. Calcif Tissue Int. 1996 Oct;59(4):235–237. [PubMed]
  • Uitterlinden AG, Pols HA, Burger H, Huang Q, Van Daele PL, Van Duijn CM, Hofman A, Birkenhäger JC, Van Leeuwen JP. A large-scale population-based study of the association of vitamin D receptor gene polymorphisms with bone mineral density. J Bone Miner Res. 1996 Sep;11(9):1241–1248. [PubMed]
  • Peacock M. Vitamin D receptor gene alleles and osteoporosis: a contrasting view. J Bone Miner Res. 1995 Sep;10(9):1294–1297. [PubMed]
  • Schwartz BS, Stewart WF, Todd AC, Links JM. Predictors of dimercaptosuccinic acid chelatable lead and tibial lead in former organolead manufacturing workers. Occup Environ Med. 1999 Jan;56(1):22–29. [PMC free article] [PubMed]
  • Stewart WF, Schwartz BS, Simon D, Bolla KI, Todd AC, Links J. Neurobehavioral function and tibial and chelatable lead levels in 543 former organolead workers. Neurology. 1999 May 12;52(8):1610–1617. [PubMed]
  • Somervaille LJ, Chettle DR, Scott MC, Aufderheide AC, Wallgren JE, Wittmers LE, Jr, Rapp GR., Jr Comparison of two in vitro methods of bone lead analysis and the implications for in vivo measurements. Phys Med Biol. 1986 Nov;31(11):1267–1274. [PubMed]
  • Kim R, Aro A, Rotnitzky A, Amarasiriwardena C, Hu H. K x-ray fluorescence measurements of bone lead concentration: the analysis of low-level data. Phys Med Biol. 1995 Sep;40(9):1475–1485. [PubMed]
  • Kim R, Landrigan C, Mossmann P, Sparrow D, Hu H. Age and secular trends in bone lead levels in middle-aged and elderly men: three-year longitudinal follow-up in the Normative Aging Study. Am J Epidemiol. 1997 Oct 1;146(7):586–591. [PubMed]
  • Kosnett MJ, Becker CE, Osterloh JD, Kelly TJ, Pasta DJ. Factors influencing bone lead concentration in a suburban community assessed by noninvasive K x-ray fluorescence. JAMA. 1994 Jan 19;271(3):197–203. [PubMed]
  • Hu H, Payton M, Korrick S, Aro A, Sparrow D, Weiss ST, Rotnitzky A. Determinants of bone and blood lead levels among community-exposed middle-aged to elderly men. The normative aging study. Am J Epidemiol. 1996 Oct 15;144(8):749–759. [PubMed]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Science