Skip to main content

Advertisement

SpringerLink
Log in

Association between polymorphisms in vitamin D receptor gene and adolescent idiopathic scoliosis: a meta-analysis

  • Original Article
  • Published:
European Spine Journal Aims and scope Submit manuscript

Abstract

Purpose

This meta-analysis was performed to clarify whether the two single nucleotide polymorphisms (ApaI and BsmI) in vitamin D receptor (VDR) gene conferred susceptibility to adolescent idiopathic scoliosis (AIS).

Methods

A comprehensive literature search in five online databases (PubMed, EMBASE, ISI Web of Science, CNKI, and Wanfang) was performed to identify studies that analyzed the association between VDR gene polymorphisms and risk of AIS. Observational studies met the predetermined inclusion criteria were selected for meta-analysis. The most appropriate genetic model was identified using a genetic model-free approach. Meta-analysis was performed using RevMan 5.3 software.

Results

Five eligible studies were included in this meta-analysis, which involved a total of 717 cases and 554 controls. A statistically significant association was observed between BsmI polymorphism and AIS (OR 1.90, 95% CI 1.32, 2.62). In subgroup analysis by ethnicity, the association between BsmI polymorphism and AIS was significant in Asians (OR 2.06, 95% CI 1.56, 2.73) but not in Caucasians (OR 0.70, 95% CI 0.23, 2.19). However, the ApaI polymorphism was not associated with AIS. Moreover, no evidence of association between BMD and the two VDR gene polymorphisms was detected.

Conclusions

Meta-analysis of existing data suggested that BsmI was associated with increased risk of AIS in Asian populations. Nevertheless, further studies with rigorous design and more ethnic groups are encouraged to validate our findings.

Graphical abstract

These slides can be retrieved under Electronic Supplementary Material.

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
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Cheng JC, Castelein RM, Chu WC, Danielsson AJ, Dobbs MB, Grivas TB, Gurnett CA, Luk KD, Moreau A, Newton PO, Stokes IA, Weinstein SL, Burwell RG (2015) Adolescent idiopathic scoliosis. Nat Rev Dis Primers 1:15030. https://doi.org/10.1038/nrdp.2015.30

    Article  PubMed  Google Scholar 

  2. Latalski M, Danielewicz-Bromberek A, Fatyga M, Latalska M, Krober M, Zwolak P (2017) Current insights into the aetiology of adolescent idiopathic scoliosis. Arch Orthop Trauma Surg. https://doi.org/10.1007/s00402-017-2756-1

    Article  PubMed  PubMed Central  Google Scholar 

  3. Weinstein SL, Dolan LA, Cheng JC, Danielsson A, Morcuende JA (2008) Adolescent idiopathic scoliosis. Lancet 371(9623):1527–1537. https://doi.org/10.1016/S0140-6736(08)60658-3

    Article  PubMed  Google Scholar 

  4. Miller NH (2002) Genetics of familial idiopathic scoliosis. Clin Orthop Relat Res 401:60–64

    Article  Google Scholar 

  5. Justice CM, Miller NH, Marosy B, Zhang J, Wilson AF (2003) Familial idiopathic scoliosis: evidence of an X-linked susceptibility locus. Spine 28(6):589–594. https://doi.org/10.1097/01.BRS.0000049940.39801.E6

    Article  PubMed  Google Scholar 

  6. Liu XY, Wang L, Yu B, Zhuang QY, Wang YP (2015) Expression signatures of long noncoding RNAs in adolescent idiopathic scoliosis. Biomed Res Int 2015:276049. https://doi.org/10.1155/2015/276049

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Lombardi G, Akoume MY, Colombini A, Moreau A, Banfi G (2011) Biochemistry of adolescent idiopathic scoliosis. Adv Clin Chem 54:165–182

    Article  PubMed  CAS  Google Scholar 

  8. Ogilvie J (2010) Adolescent idiopathic scoliosis and genetic testing. Curr Opin Pediatr 22(1):67–70. https://doi.org/10.1097/MOP.0b013e32833419ac

    Article  PubMed  Google Scholar 

  9. Chen S, Zhao L, Roffey DM, Phan P, Wai EK (2014) Association of rs11190870 near LBX1 with adolescent idiopathic scoliosis in East Asians: a systematic review and meta-analysis. Spine J Off J N Am Spine Soc 14(12):2968–2975. https://doi.org/10.1016/j.spinee.2014.05.019

    Article  Google Scholar 

  10. Gorman KF, Julien C, Moreau A (2012) The genetic epidemiology of idiopathic scoliosis. Eur Spine J 21(10):1905–1919. https://doi.org/10.1007/s00586-012-2389-6

    Article  PubMed  PubMed Central  Google Scholar 

  11. Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA, Van Leeuwen JP (2004) Genetics and biology of vitamin D receptor polymorphisms. Gene 338(2):143–156. https://doi.org/10.1016/j.gene.2004.05.014

    Article  PubMed  CAS  Google Scholar 

  12. Yamamoto Y, Yoshizawa T, Fukuda T, Shirode-Fukuda Y, Yu T, Sekine K, Sato T, Kawano H, Aihara K, Nakamichi Y, Watanabe T, Shindo M, Inoue K, Inoue E, Tsuji N, Hoshino M, Karsenty G, Metzger D, Chambon P, Kato S, Imai Y (2013) Vitamin D receptor in osteoblasts is a negative regulator of bone mass control. Endocrinology 154(3):1008–1020. https://doi.org/10.1210/en.2012-1542

    Article  PubMed  CAS  Google Scholar 

  13. Carlberg C, Molnar F (2015) Vitamin D receptor signaling and its therapeutic implications: genome-wide and structural view. Can J Physiol Pharmacol 93(5):311–318. https://doi.org/10.1139/cjpp-2014-0383

    Article  PubMed  CAS  Google Scholar 

  14. Saccone D, Asani F, Bornman L (2015) Regulation of the vitamin D receptor gene by environment, genetics and epigenetics. Gene 561(2):171–180. https://doi.org/10.1016/j.gene.2015.02.024

    Article  PubMed  CAS  Google Scholar 

  15. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G (2016) Vitamin D: metabolism, Molecular mechanism of action, and pleiotropic effects. Physiol Rev 96(1):365–408. https://doi.org/10.1152/physrev.00014.2015

    Article  PubMed  CAS  Google Scholar 

  16. Ryan JW, Anderson PH, Turner AG, Morris HA (2013) Vitamin D activities and metabolic bone disease. Clin Chim Acta 425:148–152. https://doi.org/10.1016/j.cca.2013.07.024

    Article  PubMed  CAS  Google Scholar 

  17. Anderson PH, Lam NN, Turner AG, Davey RA, Kogawa M, Atkins GJ, Morris HA (2013) The pleiotropic effects of vitamin D in bone. J Steroid Biochem Mol Biol 136:190–194. https://doi.org/10.1016/j.jsbmb.2012.08.008

    Article  PubMed  CAS  Google Scholar 

  18. Morris HA (2014) Vitamin D activities for health outcomes. Ann Lab Med 34(3):181–186. https://doi.org/10.3343/alm.2014.34.3.181

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Haussler MR, Jurutka PW, Mizwicki M, Norman AW (2011) Vitamin D receptor (VDR)-mediated actions of 1 alpha, 25(OH)(2)vitamin D(3): genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab 25(4):543–559. https://doi.org/10.1016/j.beem.2011.05.010

    Article  PubMed  CAS  Google Scholar 

  20. Blomberg Jensen M (2014) Vitamin D and male reproduction. Nat Rev Endocrinol 10(3):175–186. https://doi.org/10.1038/nrendo.2013.262

    Article  PubMed  CAS  Google Scholar 

  21. Blomberg Jensen M, Dissing S (2012) Non-genomic effects of vitamin D in human spermatozoa. Steroids 77(10):903–909. https://doi.org/10.1016/j.steroids.2012.02.020

    Article  PubMed  CAS  Google Scholar 

  22. Suh KT, Eun IS, Lee JS (2010) Polymorphism in vitamin D receptor is associated with bone mineral density in patients with adolescent idiopathic scoliosis. Eur Spine J 19(9):1545–1550

    Article  PubMed  PubMed Central  Google Scholar 

  23. Wang Y, Cui ZQ, Luo TB, Liu L (2016) Correlations of VDR and VDBP genetic polymorphisms with susceptibility to adolescent idiopathic scoliosis and efficacy of brace treatment. Genomics 108(5–6):194–200

    Article  PubMed  CAS  Google Scholar 

  24. Yilmaz H, Zateri C, Uludag A, Bakar C, Kosar S, Ozdemir O (2012) Single-nucleotide polymorphism in Turkish patients with adolescent idiopathic scoliosis: curve progression is not related with MATN-1, LCT C/T-13910, and VDR BsmI. J Orthop Res 30(9):1459–1463

    Article  PubMed  CAS  Google Scholar 

  25. Ryckman K, Williams SM (2008) Calculation and use of the Hardy-Weinberg model in association studies. Curr Protoc Hum Genet. https://doi.org/10.1002/0471142905.hg0118s57

    Article  PubMed  Google Scholar 

  26. Lewis CM, Knight J (2012) Introduction to genetic association studies. Cold Spring Harb Protoc 3:297–306. https://doi.org/10.1101/pdb.top068163

    Article  Google Scholar 

  27. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P The Newcastle–Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed 1 June 2017

  28. Thakkinstian A, McElduff P, D’Este C, Duffy D, Attia J (2005) A method for meta-analysis of molecular association studies. Stat Med 24(9):1291–1306. https://doi.org/10.1002/sim.2010

    Article  PubMed  Google Scholar 

  29. Chen WJ, Qiu Y, Zhu F, Zhu ZZ, Sun X, Liu Z, Chen ZJ (2008) Vitamin D receptor gene polymorphisms: no association with low bone mineral density in adolescent idiopathic scoliosis girls. Chin J Surg 46(15):1183–1186

    PubMed  Google Scholar 

  30. Xia CW, Qiu Y, Sun X, Qiu XS, Wang SF, Zhu ZZ, Zhu F (2007) Vitamin D receptor gene polymorphisms in female adolescent idiopathic scoliosis patients. Natl Med J China 87(21):1465–1469

    CAS  Google Scholar 

  31. Mullin GE, Dobs A (2007) Vitamin D and its role in cancer and immunity: a prescription for sunlight. Nutr Clin Pract 22(3):305–322. https://doi.org/10.1177/0115426507022003305

    Article  PubMed  Google Scholar 

  32. Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, Haussler CA, Galligan MA, Thatcher ML, Encinas Dominguez C, Haussler MR (2001) Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol 177(1–2):145–159

    Article  PubMed  CAS  Google Scholar 

  33. Chang B, Schlussel Y, Sukumar D, Schneider SH, Shapses SA (2015) Influence of Vitamin D and estrogen receptor gene polymorphisms on calcium absorption: BsmI predicts a greater decrease during energy restriction. Bone 81:138–144. https://doi.org/10.1016/j.bone.2015.07.011

    Article  PubMed  CAS  Google Scholar 

  34. Cheng JC, Qin L, Cheung CS, Sher AH, Lee KM, Ng SW, Guo X (2000) Generalized low areal and volumetric bone mineral density in adolescent idiopathic scoliosis. J Bone Miner Res 15(8):1587–1595. https://doi.org/10.1359/jbmr.2000.15.8.1587

    Article  PubMed  CAS  Google Scholar 

  35. Pourabbas Tahvildari B, Erfani MA, Nouraei H, Sadeghian M (2014) Evaluation of bone mineral status in adolescent idiopathic scoliosis. Clin Orthop Surg 6(2):180–184. https://doi.org/10.4055/cios.2014.6.2.180

    Article  PubMed  PubMed Central  Google Scholar 

  36. Ralston SH, de Crombrugghe B (2006) Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev 20(18):2492–2506. https://doi.org/10.1101/gad.1449506

    Article  PubMed  CAS  Google Scholar 

  37. Rizzoli R, Bonjour JP, Ferrari SL (2001) Osteoporosis, genetics and hormones. J Mol Endocrinol 26(2):79–94

    Article  PubMed  CAS  Google Scholar 

  38. Sandhu SK, Hampson G (2011) The pathogenesis, diagnosis, investigation and management of osteoporosis. J Clin Pathol 64(12):1042–1050. https://doi.org/10.1136/jcp.2010.077842

    Article  PubMed  CAS  Google Scholar 

  39. Lonstein JE, Carlson JM (1984) The prediction of curve progression in untreated idiopathic scoliosis during growth. J Bone Jt Surg Am 66(7):1061–1071

    Article  CAS  Google Scholar 

  40. Grivas TB, Vasiliadis E, Mouzakis V, Mihas C, Koufopoulos G (2006) Association between adolescent idiopathic scoliosis prevalence and age at menarche in different geographic latitudes. Scoliosis 1:9. https://doi.org/10.1186/1748-7161-1-9

    Article  PubMed  PubMed Central  Google Scholar 

  41. Zhang H, Guo C, Tang M, Liu S, Li J, Guo Q, Chen L, Zhu Y, Zhao S (2015) Prevalence of scoliosis among primary and middle school students in Mainland China: a systematic review and meta-analysis. Spine 40(1):41–49. https://doi.org/10.1097/BRS.0000000000000664

    Article  PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Jun Dai and Zheng-tao Lv have contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Qiaokou District, Wuhan, 430030, China

    Jun Dai, Zheng-tao Lv, Jun-ming Huang, Peng Cheng, Huang Fang & An-min Chen

Authors
  1. Jun Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zheng-tao Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jun-ming Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Peng Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Huang Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. An-min Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Huang Fang or An-min Chen.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (PPTX 455 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dai, J., Lv, Zt., Huang, Jm. et al. Association between polymorphisms in vitamin D receptor gene and adolescent idiopathic scoliosis: a meta-analysis. Eur Spine J 27, 2175–2183 (2018). https://doi.org/10.1007/s00586-018-5614-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00586-018-5614-0

Keywords

Search

Navigation