Journal of Bone and Mineral Metabolism

, Volume 29, Issue 1, pp 54–61 | Cite as

Vitamin D receptor gene polymorphism and bone mineral density in 0–6-year-old Han children

  • Xiao-Dan Yu
  • Xiao-Ming Shen
  • Ming-Bao Xue
  • Chong-Huai Yan
Original Article

Abstract

This study aims to investigate the four vitamin D receptor (VDR) gene single nucleotide polymorphisms and their possible relationship with bone mineral density (BMD) in Chinese 0–6-year-old Han children. Two hundred four 0–6-year-old Han children without metabolic bone disease were randomly recruited in Shanghai, China. The BMD of the middle tibia was measured by an ultrasonic bone density instrument. VDR genotypes were determined by polymerase chain reaction restriction fragment length polymorphism using endonuclease ApaI, BsmI, TaqI and FokI. The alleles of a, T, b and F and the genotypes of aa, TT, bb and Ff were predominant. The frequency alleles of a, T, b and F were, respectively, 70.6, 95.8, 95.3 and 57.6%. When the influences of confounders such as serum 25(OH)D, serum zinc and outdoor activities on BMD were removed, the genotypes of BsmI and FokI were found apparently to be related to BMD. The BMD of the Bb carrier was much lower than that of the bb carrier (22.00 ± 27.84 and 43.14 ± 31.98, P < 0.05). The BMD of the ff carrier was lower than that of the Ff or FF carrier (26.97 ± 34.22 and 37.95 ± 29.70 and 53.52 ± 30.35, P < 0.001), while the genotypes of ApaI and TaqI have no relation with BMD in 0–6-year-old Han children. These findings show that the Bb and ff genotypes of the VDR BsmI and FokI variants are significantly associated with a decreased BMD in Chinese Han children aged 0–6 years, while the VDR ApaI and TaqI polymorphisms are not significantly associated with it.

Keywords

Han Chinese children Vitamin D receptor Gene polymorphism Bone mineral density 

Notes

Acknowledgments

This work was supported by a Chinese National Natural Science Foundation Grant (no. 30600496).

References

  1. 1.
    Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV, Sambrook PN, Eisman JA (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367:284–287CrossRefPubMedGoogle Scholar
  2. 2.
    Minamitani K, Takahashi Y, Minagawa M, Yasuda T, Niimi H (1998) Difference in height associated with a translation start site polymorphism in the vitamin D receptor gene. Pediatr Res 44:628CrossRefPubMedGoogle Scholar
  3. 3.
    Hennig BJ, Parkhill JM, Chapple IL, Heasman PA, Taylor JJ (1999) Association of a vitamin D receptor gene polymorphism with localized early-onset periodontal diseases. J Periodontol 70:1032CrossRefPubMedGoogle Scholar
  4. 4.
    Zmuda JM, Cauley JA, Ferell RE (2000) Molecular epidemiology of vitamin D receptor gene variants. Epidemiol Rev 22:203–217PubMedGoogle Scholar
  5. 5.
    Falchetti A, Sferrazza C, Cepollaro C, Gozzini A, Del Monte F, Masi L, Napoli N, Di Fede G, Cannone V, Cusumano G, Pandolfo MC, Rini GB, Tanini A, Brandi ML (2007) FokI polymorphism of the vitamin D receptor gene correlates with parameters of bone mass and turnover in a female population of the Italian island of Lampedusa. Calcif Tissue Int 80:15–20CrossRefPubMedGoogle Scholar
  6. 6.
    Bezerra FF, Cabello GM, Mendonça LM, Donangelo CM (2008) Bone mass and breast milk calcium concentration are associated with vitamin D receptor gene polymorphisms in adolescent mothers. J Nutr 138:277–281PubMedGoogle Scholar
  7. 7.
    Wood RJ, Fleet JC (1998) The genetics of osteoporosis: vitamin D receptor polymorphisms. Annu Rev Nutr 18:33–258CrossRefGoogle Scholar
  8. 8.
    Abrams SA, Griffin IJ, Hawthorne KM, Chen Z, Gunn SK, Wilde M, Darlington G, Shypailo RJ, Ellis KJ (2005) Vitamin D receptor Fok1 polymorphisms affect calcium absorption, kinetics, and bone mineralization rates during puberty. J Bone Miner Res 20:945–953CrossRefPubMedGoogle Scholar
  9. 9.
    Laaksonen MM, Kärkkäinen MU, Outila TA, Rita HJ, Lamberg-Allardt CJ (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 22:479–485CrossRefPubMedGoogle Scholar
  10. 10.
    Strandberg S, Nordström P, Lorentzon R, Lorentzon M (2003) Vitamin D receptor start codon polymorphism (FokI) is related to bone mineral density in healthy adolescent boys. J Bone Miner Metab 21:109–113CrossRefPubMedGoogle Scholar
  11. 11.
    Lorentzon M, Lorentzon R, Nordstrom P (2001) Vitamin D receptor gene polymorphism is related to bone density, circulating osteocalcin and parathyroid hormone in healthy adolescent girls. J Bone Miner Metab 19:302–307CrossRefPubMedGoogle Scholar
  12. 12.
    Zhang C, Wang C, Liang J, Zhou X, Zheng F, Fan Y, Shi Q (2008) The vitamin D receptor Fok1 polymorphism and bone mineral density in Chinese children. Clin Chim Acta 395:111–114CrossRefPubMedGoogle Scholar
  13. 13.
    Sainz J, Van Tornout JM, Loro ML, Sayre J, Roe TF, Gilsanz V (1997) Vitamin D-receptor gene polymorphisms and bone density in prepubertal American girls of Mexican descent. N Engl J Med 337:77–82CrossRefPubMedGoogle Scholar
  14. 14.
    Cusack S, Mølgaard C, Michaelsen KF, Jakobsen J, Lamberg-Allardt CJ, Cashman KD (2006) Vitamin D and estrogen receptor—a genotype and indices of bone mass and bone turnover in Danish girls. J Bone Miner Metab 24:329–336CrossRefPubMedGoogle Scholar
  15. 15.
    Terpstra L, Knol DL, Van Coeverden SC, Delemarre-van de Waal HA (2006) Bone metabolism markers predict increase in bone mass, height and sitting height during puberty depending on the VDR FokI genotype. Clin Endocrinol (Oxf) 64:625–631CrossRefGoogle Scholar
  16. 16.
    Nakamura O, Ishii T, Ando Y, Amagai H, Oto M, Imafuji T, Tokuyama K (2002) Potential role of vitamin D receptor gene polymorphism in determining bone phenotype in young male athletes. J Appl Physiol 93:1973–1979PubMedGoogle Scholar
  17. 17.
    Rabon-Stith KM, Hagberg JM, Phares DA, Kostek MC, Delmonico MJ, Roth SM, Ferrell RE, Conway JM, Ryan AS, Hurley BF (2005) Vitamin D receptor FokI genotype influences bone mineral density response to strength training, but not aerobic training. Exp Physiol 90:653–661CrossRefPubMedGoogle Scholar
  18. 18.
    Hollis BW, Kamerud JQ, Selvaag SR, Lorenz JD (1993) Determination of vitamin D status by radioimmunoassay with a 125I-labeled tracer. Clin Chem 39:529–533PubMedGoogle Scholar
  19. 19.
    Riggs BL, Nguyen TV, Melton LJ 3rd, Morrison NA, O’Fallon WM, Kelly PL, Egan KS, Sambrook PN, Muhs JM, Eisman JA (1995) The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic women. J Bone Miner Res 10:991–996CrossRefPubMedGoogle Scholar
  20. 20.
    Sinotte M, Rousseau F, Ayotte P, Dewailly E, Diorio C, Giguère Y, Bérubé S, Brisson J (2008) Vitamin D receptor polymorphisms (FokI, BsmI) and breast cancer risk: association replication in two case-control studies within French Canadian population. Endocr Relat Cancer 15:975–983CrossRefPubMedGoogle Scholar
  21. 21.
    Fischer PR, Thacher TD, Pettifor JM, Jorde LB, Eccleshall TR, Feldman D (2000) Vitamin D receptor polymorphisms and nutritional rickets in Nigerian children. J Bone Miner Res 15:2206–2210CrossRefPubMedGoogle Scholar
  22. 22.
    Li C, Li Y, Gao LB, Wang YY, Zhou B, Lv ML, Lu HM, Zhang L (2009) Vitamin D receptor gene polymorphisms and the risk of colorectal cancer in a Chinese population. Dig Dis Sci 54:634–639CrossRefPubMedGoogle Scholar
  23. 23.
    Jin N, Lin S, Zhang Y, Chen F (2009) Assess the discrimination of Achilles InSight calcaneus quantitative ultrasound device for osteoporosis in Chinese women: compared with dual energy X-ray absorptiometry measurements. Eur J Radiol [Epub ahead of print]Google Scholar
  24. 24.
    Moayyeri A, Kaptoge S, Dalzell N, Bingham S, Luben RN, Wareham NJ, Reeve J, Khaw KT (2009) Is QUS or DXA better for predicting the 10-year absolute risk of fracture? J Bone Miner Res 24:1319–1325CrossRefPubMedGoogle Scholar
  25. 25.
    Mann TS, McGregor AH, Patel R (2008) The correlation between phalangeal quantitative ultrasonography and dual energy X-ray absorptiometry in women with premature ovarian failure. Mcgill J Med 11:132–140PubMedGoogle Scholar
  26. 26.
    Baroncelli GI, Federico G, Bertelloni S, de Terlizzi F, Cadossi R, Saggese G (2001) Bone quality assessment by quantitative ultrasound of proximal phalanxes of the hand in healthy subjects aged 3–21 years. Pediatr Res 49:713–718CrossRefPubMedGoogle Scholar
  27. 27.
    Miyatake N, Muta H, Murota C, Haga M, Fujii M (2002) Bone status assessment in Japanese subjects using speed of sound along the tibia. Chin Med J (Engl) 115:254–257Google Scholar
  28. 28.
    Diogenes ME, Bezerra FF, Cabello GM, Cabello PH, Mendonça LM, Oliveira Júnior AV (2010) Vitamin D receptor gene FokI polymorphisms influence bone mass in adolescent football (soccer) players. Eur J Appl Physiol 108(1):31–38CrossRefPubMedGoogle Scholar
  29. 29.
    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 13:925–930CrossRefPubMedGoogle Scholar
  30. 30.
    Gross C, Krishnan AV, Malloy PJ, Eccleshall TR, Zhao XY, Feldman D (1998) The vitamin D receptor gene start codon polymorphism: a functional analysis of FokI variants. J Bone Miner Res 13:1691–1699CrossRefPubMedGoogle Scholar
  31. 31.
    Arai H, Miyamoto K, Taketani Y, Yamamoto H, Iemori Y, Morita K, Tonai T, Nishisho T, Mori S, Takeda E (1997) A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. J Bone Miner Res 12:915–921CrossRefPubMedGoogle Scholar
  32. 32.
    Ames SK, Ellis KJ, Gunn SK, Copeland KC, Abrams SA (1999) Vitamin D receptor gene Fok1 polymorphism predicts calcium absorption and bone mineral density in children. J Bone Miner Res 14:740–746CrossRefPubMedGoogle Scholar
  33. 33.
    Zambrano-Morales M, Borjas L, Fernández E, Zabala W, de Romero P, Pineda L, Morales-Machín A (2008) Association of the vitamin D receptor gene BBAAtt haplotype with osteoporosis in post-menopausic women. Invest Clin 49:29–38PubMedGoogle Scholar
  34. 34.
    Dundar U, Solak M, Kavuncu V, Ozdemir M, Cakir T, Yildiz H, Evcik D (2009) Evidence of association of vitamin D receptor ApaI gene polymorphism with bone mineral density in postmenopausal women with osteoporosis. Clin Rheumatol 28:1187–1191CrossRefPubMedGoogle Scholar
  35. 35.
    Funakoshi Y, Omori H, Katoh T (2009) Association between bone mineral density and lifestyle factors or vitamin D receptor gene polymorphism in adult male workers: a cross-sectional study. Environ Health Prev Med 14:328–335CrossRefPubMedGoogle Scholar
  36. 36.
    Langdahl BL, Gravholt CH, Brixen K, Eriksen EF (2000) Polymorphisms in the vitamin D receptor gene and bone mass, bone turnover and osteoporotic fractures. Eur J Clin Invest 30:608–617CrossRefPubMedGoogle Scholar
  37. 37.
    Rezende VB, Barbosa F Jr, Montenegro MF, Sandrim VC, Gerlach RF, Tanus-Santos JE (2007) An interethnic comparison of the distribution of vitamin D receptor genotypes and haplotypes. Clin Chim Acta 384:155–159CrossRefPubMedGoogle Scholar
  38. 38.
    Heaney RP (2007) How should we evaluate bone mass in children? J Bone Miner Res 22:1313CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society for Bone and Mineral Research and Springer 2010

Authors and Affiliations

  • Xiao-Dan Yu
    • 1
  • Xiao-Ming Shen
    • 1
  • Ming-Bao Xue
    • 1
  • Chong-Huai Yan
    • 1
  1. 1.Shanghai Institute of Pediatric Research, Xinhua HospitalMedical School of Shanghai Jiaotong UniversityShanghaiChina

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