Skip to main content
SpringerLink
Log in

Association between vitamin D receptor gene polymorphisms and bone mineral density in Chinese women

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Vitamin D receptor (VDR) is implicated in the regulation of bone mineral density (BMD). In this study, we performed a meta-analysis to evaluate the association between the VDR BsmI (rs1544410) and ApaI (rs7975232) polymorphisms and BMD in Chinese women. Literature was retrieved from PubMed and other databases. The studies on the association between VDR BsmI and ApaI genotypes and BMD at the lumbar spine, the femoral neck, the trochanter or the Ward’s triangle in Han Chinese women were included in this meta-analysis. Pooled BMD differences and 95% confidence intervals (CIs) were calculated using random- or fixed- effects model. Twenty-five eligible studies, which included 4,075 Chinese women, were identified. No significant difference was observed for either genotype when the meta-analysis was limited to premenopausal women. In postmenopausal women, BMD differences were significant for BB vs. Bb [−0.029 (95% CI −0.056, −0.002) g/m2, P = 0.037] at the femoral neck, AA vs. Aa [−0.029 (95% CI −0.051, −0.006) g/m2, P = 0.012] at the lumbar spine, and Aa vs. aa [0.022(95% CI 0.011, 0.033) g/m2, P = 0.000] at the trochanter. These results suggest a modest but statistically significant association between VDR BsmI and ApaI polymorphisms and BMD in Chinese postmenopausal women, with higher BMD in heterozygous subjects. More epidemiological and mechanistic studies are needed to further investigate the role of VDR gene polymorphisms in regulating BMD and osteoporosis in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Riggs BL, Melton LJ III (1986) Involutional osteoporosis. N Engl J Med 314:1676–1686

    Article  PubMed  CAS  Google Scholar 

  2. Cummings SR, Kelsey JL, Nevitt MC, O’Dowd KJ (1985) Epidemiology of osteoporosis and osteoporotic fractures. Epidemiol Rev 7:178–208

    PubMed  CAS  Google Scholar 

  3. Kanis JA, Melton LJ III, Christiansen C, Johnston CC, Khaltaev N (1994) The diagnosis of osteoporosis. J Bone Miner Res 9:1137–1141

    Article  PubMed  CAS  Google Scholar 

  4. NIH Consensus Development Panel (2001) Osteoporosis prevention, diagnosis, and therapy. JAMA 285:785–795

    Google Scholar 

  5. Wang C (2011) Genetic association studies: hypertension and beyond. Hypertens Res 34:294–295

    Article  PubMed  CAS  Google Scholar 

  6. Albagha OM, Ralston SH (2006) Genetics and osteoporosis. Rheum Dis Clin North Am 32:659–680

    Article  PubMed  Google Scholar 

  7. Hosoi T (2010) Genetic aspects of osteoporosis. J Bone Miner Metab 28:601–607

    Article  PubMed  CAS  Google Scholar 

  8. Cheung CL, Xiao SM, Kung AW (2010) Genetic epidemiology of age-related osteoporosis and its clinical applications. Nat Rev Rheumatol 6:507–517

    Article  PubMed  Google Scholar 

  9. Ralston SH (2010) Genetics of osteoporosis. Ann N Y Acad Sci 1192:181–189

    Article  PubMed  CAS  Google Scholar 

  10. Ferrari S (2008) Human genetics of osteoporosis. Best Pract Res Clin Endocrinol Metab 22:723–735

    Article  PubMed  CAS  Google Scholar 

  11. Ralston SH, de Crombrugghe B (2006) Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev 20:2492–2506

    Article  PubMed  CAS  Google Scholar 

  12. Fang Y, van Meurs JB, d’Alesio A, Jhamai M, Zhao H, Rivadeneira F et al (2005) Promoter and 3′-untranslated-region haplotypes in the vitamin d receptor gene predispose to osteoporotic fracture: the Rotterdam study. Am J Hum Genet 77:807–823

    Article  PubMed  CAS  Google Scholar 

  13. Gennari L, Merlotti D, De Paola V, Calabro A, Becherini L, Martini G et al (2005) Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am J Epidemiol 161:307–320

    Article  PubMed  CAS  Google Scholar 

  14. Ioannidis JP, Ralston SH, Bennett ST, Brandi ML, Grinberg D, Karassa FB et al (2004) Differential genetic effects of ESR1 gene polymorphisms on osteoporosis outcomes. JAMA 292:2105–2114

    Article  PubMed  CAS  Google Scholar 

  15. Ioannidis JP, Stavrou I, Trikalinos TA, Zois C, Brandi ML, Gennari L et al (2002) Association of polymorphisms of the estrogen receptor alpha gene with bone mineral density and fracture risk in women: a meta-analysis. J Bone Miner Res 17:2048–2060

    Article  PubMed  CAS  Google Scholar 

  16. Mann V, Ralston SH (2003) Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone 32:711–717

    Article  PubMed  CAS  Google Scholar 

  17. Yamada Y (2001) Association of polymorphisms of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis. Pharmacogenetics 11:765–771

    Article  PubMed  CAS  Google Scholar 

  18. Haussler MR, Haussler CA, Bartik L, Whitfield GK, Hsieh JC, Slater S et al (2008) Vitamin D receptor: molecular signaling and actions of nutritional ligands in disease prevention. Nutr Rev 66:S98–112

    Article  PubMed  Google Scholar 

  19. Pike JW, Meyer MB (2010) The vitamin D receptor: new paradigms for the regulation of gene expression by 1,25-dihydroxyvitamin D(3). Endocrinol Metab Clin North Am 39:255–269 table of contents

    Article  PubMed  CAS  Google Scholar 

  20. Morrison NA, Qi JC, Tokita A, Kelly PJ, Crofts L, Nguyen TV et al (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367:284–287

    Article  PubMed  CAS  Google Scholar 

  21. Salamone LM, Glynn NW, Black DM, Ferrell RE, Palermo L, Epstein RS et al (1996) Determinants of premenopausal bone mineral density: the interplay of genetic and lifestyle factors. J Bone Miner Res 11:1557–1565

    Article  PubMed  CAS  Google Scholar 

  22. Garnero P, Borel O, Sornay-Rendu E, Delmas PD (1995) Vitamin D receptor gene polymorphisms do not predict bone turnover and bone mass in healthy premenopausal women. J Bone Miner Res 10:1283–1288

    Article  PubMed  CAS  Google Scholar 

  23. Fleet JC, Harris SS, Wood RJ, Dawson-Hughes B (1995) The BsmI vitamin D receptor restriction fragment length polymorphism (BB) predicts low bone density in premenopausal black and white women. J Bone Miner Res 10:985–990

    Article  PubMed  CAS  Google Scholar 

  24. Peacock M (1995) Vitamin D receptor gene alleles and osteoporosis: a contrasting view. J Bone Miner Res 10:1294–1297

    Article  PubMed  CAS  Google Scholar 

  25. Morita A, Iki M, Dohi Y, Ikeda Y, Kagamimori S, Kagawa Y et al (2004) Prediction of bone mineral density from vitamin D receptor polymorphisms is uncertain in representative samples of Japanese Women. The Japanese Population-based Osteoporosis (JPOS) Study. Int J Epidemiol 33:979–988

    Article  PubMed  Google Scholar 

  26. Eccleshall TR, Garnero P, Gross C, Delmas PD, Feldman D (1998) Lack of correlation between start codon polymorphism of the vitamin D receptor gene and bone mineral density in premenopausal French women: the OFELY study. J Bone Miner Res 13:31–35

    Article  PubMed  CAS  Google Scholar 

  27. Vandevyver C, Wylin T, Cassiman JJ, Raus J, Geusens P (1997) Influence of the vitamin D receptor gene alleles on bone mineral density in postmenopausal and osteoporotic women. J Bone Miner Res 12:241–247

    Article  PubMed  CAS  Google Scholar 

  28. Cooper GS, Umbach DM (1996) Are vitamin D receptor polymorphisms associated with bone mineral density? A meta-analysis. J Bone Miner Res 11:1841–1849

    Article  PubMed  CAS  Google Scholar 

  29. 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 19:419–428

    Article  PubMed  CAS  Google Scholar 

  30. Gong G, Stern HS, Cheng SC, Fong N, Mordeson J, Deng HW et al (1999) The association of bone mineral density with vitamin D receptor gene polymorphisms. Osteoporos Int 9:55–64

    Article  PubMed  CAS  Google Scholar 

  31. 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 Intern Med 145:255–264

    PubMed  CAS  Google Scholar 

  32. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  PubMed  CAS  Google Scholar 

  33. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22:719–748

    PubMed  CAS  Google Scholar 

  34. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  PubMed  CAS  Google Scholar 

  35. Liu L, Zhuang W, Wang C, Chen Z, Wu XT, Zhou Y (2010) Interleukin-8-251 A/T gene polymorphism and gastric cancer susceptibility: a meta-analysis of epidemiological studies. Cytokine 50:328–334

    Article  PubMed  CAS  Google Scholar 

  36. Sun L, Xi B, Yu L, Gao XC, Shi DJ, Yan YK et al (2010) Association of glutathione S-transferases polymorphisms (GSTM1 and GSTT1) with senile cataract: a meta-analysis. Invest Ophthalmol Vis Sci 51:6381–6386

    Article  PubMed  Google Scholar 

  37. Wang R, Zhong B, Liu Y, Wang C (2010) Association between alpha-adducin gene polymorphism (Gly460Trp) and genetic predisposition to salt sensitivity: a meta-analysis. J Appl Genet 51:87–94

    Article  PubMed  CAS  Google Scholar 

  38. Wang R, Zhou D, Xi B, Ge X, Zhu P, Wang B et al (2011) ENPP1/PC-1 Gene K121Q polymorphism is associated with obesity in European adult populations: evidence from a meta-analysis involving 24 324 subjects. Biomed Environ Sci 24:200–206

    PubMed  Google Scholar 

  39. Zhang S, Wang C, Xi B, Li X (2011) Association between the tumour necrosis factor-alpha-308G/A polymorphism and chronic obstructive pulmonary disease: an update. Respirology 16:107–115

    Article  PubMed  Google Scholar 

  40. Xi B, Chen J, Yang L, Wang W, Fu M, Wang C (2011) GABBR1 gene polymorphism(G1465A) is associated with temporal lobe epilepsy. Epilepsy Res 96:58–63

    Google Scholar 

  41. Tsai KS, Hsu SH, Cheng WC, Chen CK, Chieng PU, Pan WH (1996) Bone mineral density and bone markers in relation to vitamin D receptor gene polymorphisms in Chinese men and women. Bone 19:513–518

    Article  PubMed  CAS  Google Scholar 

  42. Zhao J, Zhou X, Meng X, Liu G, Xing X, Liu H et al (1997) Polymorphisms of vitamin D receptor gene and its association with bone mineral density and osteocalcin in Chinese. Chin Med J (Engl) 110:366–371

    CAS  Google Scholar 

  43. Kung AW, Yeung SS, Lau KS (1998) Vitamin D receptor gene polymorphisms and peak bone mass in southern Chinese women. Bone 22:389–393

    Article  PubMed  CAS  Google Scholar 

  44. Lau EM, Young RP, Ho SC, Woo J, Kwok JL, 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 10:226–230

    Article  PubMed  CAS  Google Scholar 

  45. Huang XY, Chu WJ, Liu YT, An XX, Chen XH (2000) An analysis of the correlation between vitamin D receptor gene polymorphisms and bone mineral density. Chin J Orthop 20:372–374

    Google Scholar 

  46. Li YL, Yang YH, Li DF, Cai XZ, Li ZW, Xu L (2000) Vitamin D receptor gene polymorphisms and bone mineral density in postmenopausal women. J Tianjin Med Univ 6:263–264

    Google Scholar 

  47. Zhang QX, Wang WJ, Qi JQ, Shen HL, Huang HX, Jiang NY (2000) Relationship between the polymorphism of vitamin D receptor gene and bone mineral density in pre- and postmenopausal women. Acad J SUMS 21:376–379

    Google Scholar 

  48. Chen HY, Chen WC, Hsu CD, Tsai FJ, Tsai CH, Li CW (2001) Relation of BsmI vitamin D receptor gene polymorphism to bone mineral density and occurrence of osteoporosis in postmenopausal Chinese women in Taiwan. Osteoporos Int 12:1036–1041

    Article  PubMed  CAS  Google Scholar 

  49. Miu YX, Zhu HM, Zhu XY, Gan JM, Chen SY (2002) Relationship between bone mineral density and polymorphism of vitamin D receptor gene in Hans in Shanghai. Chin J Osteoporos 8:20–22

    Google Scholar 

  50. Yang X, Zheng SR, Chen RJ, Chen SL, Fan ZH, Li H et al (2003) The study of relationships between genetic or environmental factors and the peak bone mineral density in Chinese Han women. Chin J Clin Obstet Gynecol 4:98–101

    Google Scholar 

  51. Zhang YY, Long JR, Liu PY, Liu YJ, Shen H, Zhao LJ et al (2003) Estrogen receptor alpha and vitamin D receptor gene polymorphisms and bone mineral density: association study of healthy pre- and postmenopausal Chinese women. Biochem Biophys Res Commun 308:777–783

    Article  PubMed  CAS  Google Scholar 

  52. He JW, Huang QR, Zhang ZL, Qin YJ, Lu JH, Li M et al (2004) Association of polymorphisms of estrogen receptor-alpha and vitamin D receptor genes with peak bone mass in Shanghai women. Chin J Endocrinol Metab 20:140–142

    CAS  Google Scholar 

  53. Wang YY, Wen XD, Li SY, Li KH, Zhou SR, Ma XM (2004) Gene polymorphisms of estrogen receptor and vitamin D receptor in postmenopausal women. Chin J Gerontol 24:888–889

    Google Scholar 

  54. Wu W, Fu ZZ (2004) The frequencies of the vitamin D receptor gene alleles and its association with bone mineral density in adults of Han nationality in Guangzhou area. Chin J Osteoporos 10:304–306

    Google Scholar 

  55. Miu YX, Zhu HM, Zhu XY (2005) Relationship between bone mineral density and polymorphism of vitamin D receptor gene in 611 Hans. Chin J Endocrinol Metab 21:448–449

    Google Scholar 

  56. Sun MD, Lin CH, Zou HB, Yang LM, Chi BR (2005) Relationships between vitamin D receptor gene polymorphism and bone metabolism indexes in pre-menopausal women of Chinese Han population in Changchun city. J Jilin Univ (Med Ed) 31:319–321

    CAS  Google Scholar 

  57. Xu MH, Liu HD, Tong XX (2005) Study of the relationship between gene polymorphism of vitamin D receptor, calcitonin receptor and bone mineral density of the Han nationality woman in Hebei. Chin J Rehabil Theory Pract 11:247–249

    Google Scholar 

  58. Xu H, Xiong DH, Xu FH, Zhang YY, Lei SF, Deng HW (2005) Association between VDR ApaI polymorphism and hip bone mineral density can be modified by body mass index: a study on postmenopausal Chinese women. Acta Biochim Biophys Sin (Shanghai) 37:61–67

    Article  CAS  Google Scholar 

  59. Dong J, Huang ZW, Piao JH, Gong J (2006) Association of bone mineral density with gene polymorphisms and environmental factors in Chinese postmenopausal women. J Hygiene Res (Wei Sheng Yan Jiu) 35:196–200

    Google Scholar 

  60. Ge JR, Li SQ, Zhu XX, Chen K (2006) Bsm I polymorphism of vitamin D receptor gene and traditional Chinese medicine differentiation type in relation to bone mineral density in female patients with postmenopausal osteoporosis. Chin J Clin Rehabil 10:42–44

    CAS  Google Scholar 

  61. Wang XL, Zhu XY, Li X, Nie YK (2007) Association of polymorphisms of estrogen receptor-alpha and vitamin D receptor genes with bone mineral density in Harbin postmenopausal women. Chin J Osteoporos 13:864–867

    CAS  Google Scholar 

  62. Wu W, Zhi XM, Li DF, Lin K, Xu L, Yang YH (2007) Relationship between bone mineral density and polymorphism of vitamin D receptor gene in postmenopausal women in Guangzhou. Chin J Pathophysiol 23:563–565

    Google Scholar 

  63. Wu W, Zhi XM, Li DF, Lin K, Xu L, Yang YH (2007) Vitamin D receptor gene polymorphism is not associated with bone mineral density of pre-menopausal women in Guangzhou. J South Med Univ (Nan Fang Yi Ke Da Xue Xue Bao) 27:364–366

    Google Scholar 

  64. Li SQ, Ge JR, Xie LH, Chen K, Xue L, Lai YL (2008) The association between Bsm I polymorphism of vitamin D receptor gene and bone mineral density in Fuzhou postmenopausal females. J Fujian Med Univ 42:259–261

    Google Scholar 

  65. Ge JR, Xie LH, Chen K, Zeng XA, Lai YL, Li SQ et al (2009) Association of genetic polymorphisms in several vitamin D receptor gene sites with bone mineral density and biochemical markers of bone turnover in postmenopausal women. J Clin Rehabil Tissue Eng Res 13:5593–5596

    CAS  Google Scholar 

  66. Laaksonen MM, Karkkainen 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 22:479–485

    Article  PubMed  CAS  Google Scholar 

  67. Arabi A, Mahfoud Z, Zahed L, El-Onsi L, El-Hajj Fuleihan G (2010) 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

    Article  PubMed  CAS  Google Scholar 

  68. Zintzaras E, Rodopoulou P, Koukoulis GN (2006) BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and the risk of osteoporosis: a meta-analysis. Dis Markers 22:317–326

    PubMed  CAS  Google Scholar 

  69. Ji GR, Yao M, Sun CY, Li ZH, Han Z (2010) BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and risk of fracture in Caucasians: a meta-analysis. Bone 47:681–686

    Article  PubMed  CAS  Google Scholar 

  70. Li WF, Hou SX, Yu B, Li MM, Ferec C, Chen JM (2010) Genetics of osteoporosis: accelerating pace in gene identification and validation. Hum Genet 127:249–285

    Article  PubMed  CAS  Google Scholar 

  71. Samelson EJ, Hannan MT (2006) Epidemiology of osteoporosis. Curr Rheumatol Rep 8:76–83

    Article  PubMed  Google Scholar 

  72. Christakos S, Dhawan P, Benn B, Porta A, Hediger M, Oh GT et al (2007) Vitamin D: molecular mechanism of action. Ann N Y Acad Sci 1116:340–348

    Article  PubMed  CAS  Google Scholar 

  73. Norman AW (2006) Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology 147:5542–5548

    Article  PubMed  CAS  Google Scholar 

  74. St-Arnaud R (2008) The direct role of vitamin D on bone homeostasis. Arch Biochem Biophys 473:225–230

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopaedics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, China

    Yufei Li & Kanghua Li

  2. Department of Maternal and Child Health Care, School of Public Health, Shandong University, Jinan, 250012, China

    Bo Xi

  3. Baylor College of Medicine and The University of Texas M. D. Anderson Cancer Center, Houston, TX, 77030, USA

    Chunyu Wang

Authors
  1. Yufei Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bo Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kanghua Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chunyu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Yufei Li or Chunyu Wang.

Additional information

Yufei Li and Bo Xi are co-first authors.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Li, Y., Xi, B., Li, K. et al. Association between vitamin D receptor gene polymorphisms and bone mineral density in Chinese women. Mol Biol Rep 39, 5709–5717 (2012). https://doi.org/10.1007/s11033-011-1380-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-011-1380-3

Keywords

Search

Navigation