Molecular Biology Reports

, Volume 39, Issue 5, pp 6243–6250

Vitamin D receptor gene variability as a factor influencing bone mineral density in pediatric patients

  • Elżbieta Jakubowska-Pietkiewicz
  • Wojciech Młynarski
  • Izabela Klich
  • Wojciech Fendler
  • Danuta Chlebna-Sokół
Article

Abstract

To determine the relationship between the polymorphism of vitamin D receptor gene and the bone mineral density in children. The study group consisted of 395 children aged 6–18 years. All patients underwent genotyping using the PCR-RFLP method within polymorphic loci BsmI (rs1544410), FokI (rs2228570), ApaI (rs7975232) and Taq I (rs731236) of the VDR gene. The BMD (g/cm2, Z score) and BMC (g, Z score) by DXA method, as well as Z scores of the BUA, SOS and Stiffness ultrasound parameters were evaluated. Based on densitometry results, children were divided into 3 groups: I—Z score ± 1.0; II—Z score from −1.1 to −2.0; and III—Z score ≤ −2.1. A control group numbering 294 children was used for the purpose of allele frequency comparisons. The occurrence of studied polymorphism alleles in the control group did not significantly differ from the values expected according to the Hardy–Weinberg equilibrium (p values: 0.1224 for BsmI; 0.5958 for TaqI; 0.0817 for ApaI; and 0.8901 for FokI). Allele a ApaI carrier status in group III children was associated with an increased BMD (x = 0.8 vs 0.69, p = 0.0296) and BMC value (x = 28.76 vs 22.14, p = 0.0565) in spine projection results, Stiffness (x = −1.12 vs −1.91, p = 0.0347) and SOS (x = −1.43 vs −2.27, p = 0.0319) ultrasound parameters. In group II, significantly increased SOS values (−1.13 vs −1.73, p = 0.0378) were noted in f (FokI) carriers. The presence of aaApaI and ffFokI polymorphisms favours a higher bone mass and better bone structure (decreased bone mass loss) in the analysed group.

Keywords

VDR polymorphism Bone mineral density (BMD) Children 

References

  1. 1.
    Baim S, Leonard MB, Bianchi ML, Hans DB, Kalkwarf HJ, Langman CB, Rauch F (2008) Official positions of the international society for clinical densitometry and executive summary of the 2007 ISCD pediatric position development conference. J Clin Densitom 11:6–21PubMedCrossRefGoogle Scholar
  2. 2.
    Pocock NA, Eisman JA, Hopper JL, Yeates MG, Sambrook PN, Eberl S (1987) Genetic determinants of bone mass in adults: a twin study. J Clin Invest 80:706–710PubMedCrossRefGoogle Scholar
  3. 3.
    Ates O, Dolek B, Muselim B, Ongen G, Topal-Sarikaya A (2011) The association between BsmI variant of vitamin D receptor gene ans susceptibility to tuberculosis. Mol Biol Rep 38:2633–2636PubMedCrossRefGoogle Scholar
  4. 4.
    Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2010) Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta analysis. Mol Biol Rep (Epub ahead of print)Google Scholar
  5. 5.
    Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA (1997) Corrections—prediction of bone density from vitamin D receptor alleles. Nature 387:106Google Scholar
  6. 6.
    Sainz J, Van Tornout JM, Loro ML, Sayre J, Roe TF, Glisanz V (1997) Vitamin D-receptor gene polymorphism and bone density in prepubertal American girls of Mexican Descent. N Engl J Med 337:77–82PubMedCrossRefGoogle Scholar
  7. 7.
    Uitterlinden AG, Pols HA, Burger H, Huang Q, Van Daele PL, Van Duijn CM, Hofman A, Birkenhager JC, Van Leeuwen JP (1996) A large-scale population-based study of the association of vitamin D receptor gene polymorphism with bone mineral density. J Bone Miner Res 9:1241–1248Google Scholar
  8. 8.
    Kruk M, Karczmarewicz E, Skorupa E, Lorenc RS (2003) Podłoże genetyczne wytrzymałości mechanicznej kości. Twój Magazyn Medyczny 6:11–17Google Scholar
  9. 9.
    Jaworski M, Lebiedowski M, Lorenc RS (1995) Pomiary gęstości kości piętowej metodą ultrasonograficzną u dzieci i młodzieży. Pol Tyg Lek 50:20–23PubMedGoogle Scholar
  10. 10.
    The Genetic Factors for Osteoporosis (GEFOS) Consortium (2009) Twenty bone mineral density loci identified by large scale meta-analysis of genome-wide association studies. Nat Genet 41:1199–1206CrossRefGoogle Scholar
  11. 11.
    Tao C, Yu T, Garnett S, Briody J, Knight J, Woodhead H, Cowell (1998) CT. Vitamin D receptor alleles predict growth and bone density in girls. Arch Dis Child 79:488–494Google Scholar
  12. 12.
    Baroncelli GI, Federico G, Bertelloni S, Ceccarelli C, Cupelli D, Saggese G (1999) Vitamin D receptor genotype does not predict bone mineral density, bone turnover, and growth in prepubertal children. Horm Res 51:150–156PubMedCrossRefGoogle Scholar
  13. 13.
    Ferrari S, Rizzoli R, Manen D, Slosman D, Bonjour JP (1998) Vitamin D receptor gene start codon polymorphisms (FokI) and bone mineral density: interaction with age, dietary calcium, and 3′-end region polymorphisms. J Bone Miner Res 13:925–930PubMedCrossRefGoogle Scholar
  14. 14.
    Abrams SA, Griffin IJ, Hawthorne KM, Chen Z, Gunn SK, Wilde M, Darlington G, Shypailo RJ, Ellis KJ (2005) Vitamin D receptor FokI polymorphisms affect calcium absorption, kinetics, and bone mineralization rates during puberty. J Bone Miner Res 20:945–953PubMedCrossRefGoogle Scholar
  15. 15.
    Zhang C, Wang C, Liang J, Zhou X, Fan Y, Shi Q (2008) The vitamin D receptor Fok 1 polymorphism and bone mineral density in Chinese children. Clin Chim Acta 395:111–114PubMedCrossRefGoogle Scholar
  16. 16.
    Willing MC, Torner JC, Burns TL, Janz KF, Marshall T, Glimore J, Deschenes SP, Warren JJ, Levy SM (2003) Gene polymorphisms, bone mineral density and bone mineral content in young children: Iowa bone development study. Osteoporos Int 14:650–658PubMedCrossRefGoogle Scholar
  17. 17.
    Cusack S, Melgaard C, Michaeles KF, Jakobsen J, Lamberg-Allardt CJ, Cashman KD (2006) Vitamin D and estrogen receptor alpha genotype and indices of bone mass and bone turnover in Danish girls. J Bone Miner Metab 24:329–336PubMedCrossRefGoogle Scholar
  18. 18.
    Hustmyer FG, Peacock M, Hui S, Johnston CC, Christian J (1994) Bone mineral density in relation to polymorphism at the vitamin D receptor gene locus. J Clin Invest 94:2130–2134PubMedCrossRefGoogle Scholar
  19. 19.
    Garnero P, Borel O, Sornay-Rendu E, Arlot ME, Delmas PD (1996) Vitamin D receptor gene polymorphism are not related to bone turnover rate of bone loss, and bone mass in postmenopausal women: the OFELY study. J Bone Miner Res 11:827–834PubMedCrossRefGoogle Scholar
  20. 20.
    Uiterlinden AG, Ralston SH, Brandi ML, Carey AH, Grinberg D, Langhahi BL, Lips P, Lorenc R et al (2006) The association between common vitamin D receptor gene variations and osteoporosis: a participant–level meta-analysis. Ann Intern Med 145:255–264Google Scholar
  21. 21.
    Omasu F, Kitagawa J, Koyama K, Asakawa K, Yokouchi J, Ando D, Nakahara Y (2004) The influence of VDR genotype and exercise on ultrasound parameters in young adult Japanese women. J Physiol Anthropol Appl Human Sci 23:49–55PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Elżbieta Jakubowska-Pietkiewicz
    • 1
  • Wojciech Młynarski
    • 2
  • Izabela Klich
    • 2
  • Wojciech Fendler
    • 2
  • Danuta Chlebna-Sokół
    • 1
  1. 1.Department of Paediatric Propedeutics and Bone Metabolism DiseasesMedical University of LodzŁódźPoland
  2. 2.Department of Pediatrics, Oncology, Hematology and DiabetologyMedical University of LodzŁódźPoland

Personalised recommendations