Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Effect of age, gender and calciotropic hormones on the relationship between vitamin D receptor gene polymorphisms and bone mineral density

Abstract

Background/Objectives:

Hypovitaminosis D is a major public health problem worldwide and unexpectedly more so in sunny countries. Vitamin D receptor (VDR) gene is associated with inter-individual variance in bone mineral density (BMD). Studies assessing the effect of VDR gene polymorphisms on BMD yielded conflicting results. The aim of this study was to assess the relationship between VDR polymorphisms and BMD in the Lebanese, across age groups and genders and to assess the effect of PTH and lean mass and vitamin D levels on such relationship.

Subjects/Methods:

In total, 203 subjects aged 65–85 years and 336 children aged 10–17 years. Polymorphisms in the VDR gene were assessed with the restriction enzymes BsmI, TaqI and ApaI. Bone mineral content, BMD and lean mass were measured using Dual-Energy X-ray Absorptiometry (DXA). The dominant hand strength was measured in children.

Results:

Heterozygote genotype was the most frequent in both age groups. There was no difference in the frequency distribution of genotypes between the young and the elderly. No relationship between VDR genotypes and lean mass was found in either age group. Heterozygote boys had the lowest parathormone (PTH) and heterozygote elderly women had the highest BMD at the spine and forearm.

Conclusions:

In the Lebanese, the relationship between VDR polymorphisms and BMD differs by age. Survival does not seem to differ by VDR genotype. However, further studies are needed to assess the effect of VDR gene polymorphisms on mortality per se and time to mortality, not evaluated in this study.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1

References

  • Abdullah M, Salhi H, Bakry L, Okamoto E, Abomelha A, Stevens B et al. (2002). Adolescent rickets in Saudi Arabia: a rich and sunny country. J Pediatr Endocrinol Metab 15, 1017–1025.

    Article  Google Scholar 

  • Ames S, Ellis K, Gunn S, Copeland K, Abrams S (1999). Vitamin D receptor gene Fok1 polymorphism predicts calcium absorption and bone mineral density in children. J Bone Miner Res 14, 740–746.

    Article  CAS  Google Scholar 

  • Arabi A, Baddoura R, Awada H, Salamoun M, Ayoub G, El-Hajj Fuleihan G (2006). Hypovitaminosis D osteopathy: is it mediated through PTH, lean mass, or is it a direct effect? Bone 39, 268–275.

    Article  CAS  Google Scholar 

  • Baroncelli G, Bereket A, El Kholy M, Audi L, Cesur Y, Ozkan B et al. (2008). Rickets in the Middle East: role of environment and genetic predisposition. J Clin Endocrinol Metab 93, 1743–1750.

    Article  CAS  Google Scholar 

  • Bischoff HA, Borchers M, Gudat F, Duermueller U, Theiler R, Stähelin HB et al. (2001). In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J 33, 19–24.

    Article  CAS  Google Scholar 

  • Bischoff-Ferrari H, Borchers M, Gdat F, Durmuller U, Stahelin H, Dick W (2004). Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 19, 265–269.

    Article  CAS  Google Scholar 

  • Chang TJ, Lei HH, Yeh JI, Chiu KC, Lee KC, Chen MC et al. (2000). Vitamin D receptor gene polymorphisms influence susceptibility to type1 diabetes mellitus in the Taiwanese population. Clinic Endocrin 52, 575–580.

    Article  CAS  Google Scholar 

  • Chapuy MC, Preziosi P, Maamer M, Arnaud S, Galan P, Hercberg S et al. (1997). Prevalence of vitamin D insufficiency in an adult normal population. Osteoporos Int 7, 439–443.

    Article  CAS  Google Scholar 

  • Duman BS, Tanakol R, Erensoy N, Ozturk M, Vilmazer S (2004). Vitamin D receptor alleles, bone mineral density and turnover in postmenopausal osteoporotic and healthy women. Med Princ Pract 13, 260–266.

    Article  Google Scholar 

  • El-Hajj Fuleihan G, Nabulsi M, Choucair M, Salamoun M, Hajj Shahine C et al. (2001). Hypovitaminosis D in healthy schoolchildren. Pediatrics 107, E53.

    Article  CAS  Google Scholar 

  • El-Hajj Fuleihan G, Nabulsi M, Tamim H, Maalouf J, Salamoun M, Khalife H et al. (2006). Effect of vitamin D replacement on musculoskeletal parameters in school children: a randomized controlled trial. J Clin Endocrinol Metab 91, 405–412.

    Article  Google Scholar 

  • El-Hajj Fuleihan G, Vieth R (2007). Vitamin D insufficiency and musculoskeletal health in children and adolescents. Int Cong Ser Elsevier 1297, 91–108.

    Article  CAS  Google Scholar 

  • Essawy M, El Kholy M, El Husseiny S Awad Z (1992). Plasma concentration of 1,25-dihydroxyvitamin D before and during treatment of vitamin D deficiency rickets. Pediatric Rev Commun 6, 145–152.

    Google Scholar 

  • Ferrari S, Rizzoli R, Slosman D, Bonjour J (1998). Do dietary calcium and age explain the controversy surrounding the relationship between bone mineral density and vitamin D receptor gene polymorphisms? J Bone Miner Res 13, 363–370.

    Article  CAS  Google Scholar 

  • Flint J, Harding R, Clegg J, Boyce A (1993). Why are some genetic diseasescommon? Distinguishing selection from other processes by molecular analysis of globin gene variants. Hum Genet 91, 91–117.

    Article  CAS  Google Scholar 

  • Gannage-Yared M, Chemali R, Yaacoub N, Halaby G (2000). Hypovitaminosis D in a sunny country: relation to lifestyle and bone markers. J Bone Miner Res 15, 1856–1862.

    Article  CAS  Google Scholar 

  • Garnero P, Munoz F, Borel O, Sornay-Rendu E, Delams P (2005). Vitamin receptor gene polymorphisms are associated with the risk of fractures in postmenopausal women, independently of bone mineral density. J Clin Endocrinol Metab 90, 4829.

    Article  CAS  Google Scholar 

  • Grundberg E, Brandstrom E, Ribom E, Ljunggren O, Mallmin H, Kindmark A (2004). Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol 150, 323–328.

    Article  CAS  Google Scholar 

  • Guesens P, Vandevyver C, Vanhoof J, Cassiman J, Boonen S, Raus J (1997). Quadriceps and grip strength are related to vitamin D receptor genotype in elderly nonobese women. J Bone Miner Res 12, 2082–2088.

    Article  Google Scholar 

  • Heist RS, Zhou W, Wang Z, Liu G, Neuberg D, Su L et al. (2008). Circulating 25-hydroxyvitamin D, VDR polymorphisms, and survival in advanced non-small-cell lung cancer. J Clin Oncol 26, 5596–5602.

    Article  CAS  Google Scholar 

  • Holick M, Chen T (2008). Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 87, 1080S–1086S.

    Article  CAS  Google Scholar 

  • Howard G, Nguyen T, Morrison N, Watanabe T, Sambrook P, Eisman J et al. (1995). Genetic influences on bone density: physiological correlates of vitamin D receptor gene alleles in premenopausal women. J Clin Endocrinol Metab 80, 2800–2805.

    CAS  PubMed  Google Scholar 

  • Hustmyer F, Peacok M, Hui S, Johnston C, Christian J (1994). Bone mineral density in relation to polymorphism at the vitamin D receptor gene locus. J Clin Invest 94, 2130–2134.

    Article  CAS  Google Scholar 

  • Keen R, Egger P, Fall C, Major P, Lanchbury J, Spector TD et al. (1997). Polymorphisms of the vitamin D receptor, infant growth, and adult bone mass. Calcif Tissue Int 60, 233–235.

    Article  CAS  Google Scholar 

  • Kimball S, El-Hajj Fuleihan G, Vieth R (2008). Vitamin D: a growing perspective. Crit Rev Clinic Lab Sci 45, 339–415.

    Article  CAS  Google Scholar 

  • Laaksonen M, Karkkainen M, Outila T, Rita H, Lamberg-Allard C (2004). Vitamin D receptor gene start codon polymorphism (FokI) is associated with forearm bone mineral density and calcaneal ultrasound in Finnish adolescent boys but not in girls. J Bone Miner Metab 22, 479–485.

    Article  CAS  Google Scholar 

  • Laaksonen M, Kärkkäinen M, Outila T, Vanninen T, Ray C, Lamberg-Allardt C (2002). Vitamin D receptor gene BsmI-polymorphism in Finnish premenopausal and postmenopausal women: its association with bone mineral density, markers of bone turnover, and intestinal calcium absorption, with adjustment for lifestyle factors. J Bone Miner Metab 20, 383–390.

    Article  CAS  Google Scholar 

  • Lau E, Young R, Ho S, Woo J, Kwok J, Birjandi Z et al. (1999). Vitamin D receptor gene polymorphisms and bone mineral density in elderly Chinese men and women in Hong Kong. Osteoporos Int 10, 226.

    Article  CAS  Google Scholar 

  • Lips P (2007). Vitamin D status and nutrition in Europe and Asia. J Steroid Biochem Mol Biol 103, 620–625.

    Article  CAS  Google Scholar 

  • Macdonald HM, McGuigan FE, Stewart A, Black AJ, Fraser WD, Ralston S et al. (2006). Large-scale population-based study shows no evidence of association between common polymorphism of the VDR gene and BMD in British women. J Bone Miner Res 21, 151–162.

    Article  CAS  Google Scholar 

  • McClure L, Eccleshall TR, Gross C, Villa M, Lin N, Ramaswamy V et al. (1997). VDR polymorphisms, bone mineral density, and bone metabolism in postmenopausal Mexican-American women. J Bone Miner Res 12, 234–240.

    Article  CAS  Google Scholar 

  • Mehrotra R, Kermah DA, Salusky IB, Wolf MS, Thadhani RI, Chiu YW et al. (2009). Chronic kidney disease, hypovitaminosis D, and mortality in the United States. Kidney Int 76, 977–983.

    Article  CAS  Google Scholar 

  • Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV (1994). Prediction of bone density from vitamin D receptor alleles. Nature 367, 284–285.

    Article  CAS  Google Scholar 

  • Nagpal S, Rathnachalam R (2005). Noncalcemic actions of vitamin D receptor ligands. Endocr Rev 26, 662–687.

    Article  CAS  Google Scholar 

  • Pilz S, Tomaschitz A, Obermayer-Pietsch B, Dobnig H, Pieber TR (2009). Epidemiology of vitamin D insufficiency and cancer mortality. Anticancer Res 29, 3699–3704.

    PubMed  Google Scholar 

  • Pottelbergh I, Goemaere S, De Bacquer D, De Paepe A, Kaufman M (2002). Vitamin D receptor gene allelic variants, bone density, and bone turnover in community-dwelling men. Bone 31, 631–637.

    Article  Google Scholar 

  • Saadi H, Nagelkerke N, Benedict S, Qazaq H, Zilahi E, Mohamadiyeh M et al. (2006). Predictors and relationships of serum 25 hydroxyvitamin D concentration with bone turnover markers, bone mineral density, and vitamin D receptor genotype in Emirati women. Bone 5, 1136–1143.

    Article  Google Scholar 

  • Staud R (2005). Vitamin D: more than just affecting calcium and bone. Curr Rheumatol Rep 7, 356–364.

    Article  CAS  Google Scholar 

  • Uitterlinden AG, Ralston SH, Brandi ML, Carey AH, Grinberg D, Langdahl BL et al. (2006). The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis. Ann Int Med 145, 255–264.

    Article  CAS  Google Scholar 

  • Zofkova I, Zajickova K, Hill M (2003). Serum parathyroid hormone levels are associated with Fok I polymorphism of the vitamin D receptor gene in untreated postmenopausal women. Eur J Int Med 14, 232–236.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The elderly study was supported by a grant from the World Health Organization-Eastern Mediterranean Region Organization (WHO-EMRO), a grant from Sanofi-Aventis, and by institutional funds from the American University of Beirut and Saint Joseph University. The school study was supported in large part by an educational grant from the Nestle Foundation and a grant from Merck KGaA. We thank the study subjects for making the study possible, Mrs C Hajj-Chahine for running the PTH and vitamin D assays, and Ms S Mroueh for the densitometry measurements.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A Arabi.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Arabi, A., Mahfoud, Z., Zahed, L. et al. Effect of age, gender and calciotropic hormones on the relationship between vitamin D receptor gene polymorphisms and bone mineral density. Eur J Clin Nutr 64, 383–391 (2010). https://doi.org/10.1038/ejcn.2010.5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2010.5

Keywords

  • bone mineral density
  • gene polymorphisms
  • vitamin D
  • vitamin D receptor
  • survival

This article is cited by

Search

Quick links