Clinical Rheumatology

, Volume 28, Issue 10, pp 1187–1191 | Cite as

Evidence of association of Vitamin D receptor Apa I gene polymorphism with bone mineral density in postmenopausal women with osteoporosis

  • Umit Dundar
  • Mustafa Solak
  • Vural Kavuncu
  • Mujgan Ozdemir
  • Tuncay Cakir
  • Handan Yildiz
  • Deniz Evcik
Original Article

Abstract

The vitamin D receptor (VDR) was the first candidate gene to be studied in relation to osteoporosis, and most attention has focused on polymorphisms situated near the 3′ flank of VDR. The aim of this study was to investigate the association about VDR gene Apa I polymorphism with bone mineral density (BMD) in postmenopausal women with osteoporosis. We studied a total of 136 postmenopausal women with a mean age of 56.36 ± 10.29 years. Among them, a total of 75 had osteoporosis, 37 had osteopenia, and 24 had normal BMD. Venous blood samples were obtained for evaluation of bone metabolism and genotyping. The VDR Apa I genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. BMDs at the lumbar spine and hip were measured by dual-energy X-ray absorptiometry. Postmenopausal women with aa genotype had significantly lower BMD values (grams per centimeter square) at lumbar spines compared to persons with AA genotype. Also, postmenopausal women with AA genotype had significantly higher serum Ca level than the subjects with aa genotype. In conclusion, our result may indicate that VDR Apa I gene polymorphism may be responsible for a important part of the heritable component of lumbar spine BMD in postmenopausal women, possibly related to impaired calcium absorption from the bowel.

Keywords

Bone mineral density Osteoporosis Vitamin D receptor Apa I gene polymorphism 

References

  1. 1.
    Kanis JA, Melton LJ, Christiansen C, Johnston CC, Khaltaev N (1994) The diagnosis of osteoporosis. J Bone Miner Res 9:1137–1141PubMedGoogle Scholar
  2. 2.
    Prince RL, Dick I (1997) Oestrogen effects on calcium membrane transport: a new view of the inter-relationship between oestrogen deficiency and age-related osteoporosis. Osteoporos Int 7(suppl 3):S150–S154PubMedGoogle Scholar
  3. 3.
    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
  4. 4.
    Christian JC, Yu PL, Slemenda CW, Johnston CC (1989) Heritability of bone mass: a longitudinal study in aging male twins. Am J Hum Genet 44:429–433PubMedGoogle Scholar
  5. 5.
    Slemenda CW, Christian JC, Williams CJ, Norton JA, Johnston CC (1991) Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J Bone Miner Res 6:561–567PubMedGoogle Scholar
  6. 6.
    Flicker L, Hopper JL, Rodgers L, Kaymakci B, Green RM, Wark JD (1995) Bone density in elderly women: a twin study. J Bone Miner Res 10:1607–1613PubMedCrossRefGoogle Scholar
  7. 7.
    Michaelsson K, Melhus H, Ferm H, Ahlbom A, Pedersen NL (2005) Genetic liability to fractures in the elderly. Arch Intern Med 165:1825–1830PubMedCrossRefGoogle Scholar
  8. 8.
    Stewart TL, Ralston SH (2000) Role of genetic factors in the pathogenesis of osteoporosis. J Endocrinol 166:235–245PubMedCrossRefGoogle Scholar
  9. 9.
    Ralston SH, de Crombrugghe B (2006) Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev 20:2492–2506PubMedCrossRefGoogle Scholar
  10. 10.
    Kristjansson K, Rut AR, Hewison M, O’Riordan JL, Hughes MR (1993) Two mutations in the hormone binding domain of the vitamin D receptor cause tissue resistance to 1,25 dihydroxyvitamin D3. J Clin Invest 92:12–16PubMedCrossRefGoogle Scholar
  11. 11.
    Zmuda JM, Cauley JA, Danielson ME, Wolf RL, Ferrell RE (1997) Vitamin D receptor gene polymorphisms, bone turnover, and rates of bone loss in older African-American women. J Bone Miner Res 12:1446–1452PubMedCrossRefGoogle Scholar
  12. 12.
    Zhang ZL, Zhao JX, Meng XW, Zhou XY, Xing XP, Xia WB (2003) Association of polymorphisms of vitamin D receptor gene start codon and 3′-end region with bone mineral density in postmenopausal women. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 20(1):5–8PubMedGoogle Scholar
  13. 13.
    Qin YJ, Zhang ZL, Huang QR, He JM, Hu YQ, Zhao Q, Lu JH, Li M, Liu YJ (2004) Association of vitamin D receptor and estrogen receptor-alpha gene polymorphism with peak bone mass and bone size in Chinese women. Acta Pharmacol Sin 25(4):462–468PubMedGoogle Scholar
  14. 14.
    Gennari L, Becherini L, Masi L, Gonnelli S, Cepollaro C, Martini S, Mansani R, Brandi ML (1997) Vitamin D receptor genotypes and ıntestinal calcium absorption in postmenopausal women. Calcif Tissue Int 61:460–463PubMedCrossRefGoogle Scholar
  15. 15.
    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(1):29–38PubMedGoogle Scholar
  16. 16.
    Huang QR, Zhang ZL, Qin YJ, He JW, Lu JH, Zhou Q, Hu YQ, Li M, Liu YJ (2003) Association of Apa I polymorphism of vitamin D receptor gene with bone mass in men. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 25(3):254–257PubMedGoogle Scholar
  17. 17.
    Williams FMK, Spector TD (2007) The genetics of osteoporosis. Acta Reumatol Port 32:231–240PubMedGoogle Scholar
  18. 18.
    Yokoyama K, Shigematsu T, Tsukada T, Ogura Y, Takemoto F, Hara S, Yamada A, Kawaguchi Y, Hosoya T (1998) Apa I polymorphism in the vitamin D receptor gene may affect the parathyroid response in Japanese with end-stage renal disease. Kidney Int 53(2):454–458PubMedCrossRefGoogle Scholar
  19. 19.
    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 12:915–921PubMedCrossRefGoogle Scholar
  20. 20.
    Zhang ZL, Qin YJ, Huang QR, He JW, Li M, Zhou Q, Hu YQ, Liu YJ (2004) Association of estrogen receptor-alpha and vitamin D receptor genotypes with therapeutic response to calcium in postmenopausal Chinese women. Acta Pharmacol Sin 25(12):1690–1697PubMedGoogle Scholar
  21. 21.
    Iki M, Saito Y, Dohi Y, Kajita E, Nishino H, Yonemasu K, Kusaka Y (2002) Greater trunk muscle torque reduces postmenopausal bone loss at the spine independently of age, body size and vitamin D receptor genotype in Japanese women. Calcif Tissue Int 71:300–307PubMedCrossRefGoogle Scholar
  22. 22.
    Bid HK, Mishra DK, Mittal R (2005) Vitamin-D receptor (VDR) gene (Fok-I, Taq-I and Apa-I) polymorphisms in healthy individuals from north Indian population. Asian Pac J Cancer Prev 6(2):147–152PubMedGoogle Scholar
  23. 23.
    Fountas L, Moutsatsou P, Kastanias I, Tamouridis N, Tzanela M, Anapliotou M, Sekeris CE (1999) The contribution of vitamin D receptor gene polymorphisms in osteoporosis and familial osteoporosis. Osteoporos Int 10(5):392–398PubMedCrossRefGoogle Scholar
  24. 24.
    Thakkinstian A, D’Este C, Eisman J, Nguyen T, Attia J (2004) Meta-analysis of molecular association studies: vitamin D receptor gene polymorphisms and BMD as a case study. J Bone Miner Res 19:419–428PubMedCrossRefGoogle Scholar

Copyright information

© Clinical Rheumatology 2009

Authors and Affiliations

  • Umit Dundar
    • 1
  • Mustafa Solak
    • 2
  • Vural Kavuncu
    • 1
  • Mujgan Ozdemir
    • 2
  • Tuncay Cakir
    • 1
  • Handan Yildiz
    • 2
  • Deniz Evcik
    • 3
  1. 1.Department of Physical Medicine and RehabilitationAfyon Kocatepe University Faculty of MedicineAfyonkarahisarTurkey
  2. 2.Medical BiologyKocatepe University Faculty of MedicineAfyonkarahisarTurkey
  3. 3.Physical Medicine and RehabilitationUfuk University Faculty of MedicineAnkaraTurkey

Personalised recommendations