Skip to main content
SpringerLink
Log in

Association between the ESR1 -351A>G single nucleotide polymorphism (rs9340799) and adolescent idiopathic scoliosis: a systematic review and meta-analysis

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

Abstract

Purpose

A single nucleotide polymorphism in the promoter region of the estrogen receptor alpha gene (ESR1), rs9340799, has been linked with adolescent idiopathic scoliosis (AIS) in several association studies with limited sample size and inconsistent findings. A systematic review can provide a comprehensive appraisal of literature evidence and a meta-analysis can obtain a more precise estimate of any association. The purpose of the present study was to assess and synthesize the currently available evidence on the association between rs9340799 and AIS by conducting a systematic review and meta-analysis.

Methods

This review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. PubMed (MEDLINE), EMBASE, Scopus and HuGE Literature Finder databases were systematically searched to identify relevant studies following a sensitive strategy. Summary odds ratios and corresponding 95 % confidence intervals (95 % CI) were estimated using the fixed-effect inverse variance model for allelic (G vs. A) and genotypic comparisons.

Results

Meta-analysis of four studies (n = 1,827 AIS cases and n = 1,253 controls) found a non-significant association between rs9340799 and AIS (allelic odds ratio 1.09, 95 % CI 0.96–1.23, p = 0.17).

Conclusions

When examined in isolation, the rs9340799 polymorphism does not appear to be a likely susceptibility variant for AIS predisposition. However, rs9340799 may be associated with AIS severity, progression and treatment; further investigation is necessary to confirm these potential associations.

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

Similar content being viewed by others

References

  1. Ogilvie J (2010) Adolescent idiopathic scoliosis and genetic testing. Curr Opin Pediatr 22:67–70

    Article  PubMed  Google Scholar 

  2. Roach JW (1999) Adolescent idiopathic scoliosis. Orthop Clin North Am 30:353–365

    Article  CAS  PubMed  Google Scholar 

  3. Rogala EJ, Drummond DS, Gurr J (1978) Scoliosis: incidence and natural history. A prospective epidemiological study. J Bone Joint Surg Am 60:173–176

    CAS  PubMed  Google Scholar 

  4. Lowe TG, Edgar M, Margulies JY, Miller NH, Raso VJ, Reinker KA, Rivard CH (2000) Etiology of idiopathic scoliosis: current trends in research. J Bone Joint Surg Am 82-A:1157–1168

    CAS  PubMed  Google Scholar 

  5. Juul A (2001) The effects of oestrogens on linear bone growth. Hum Reprod Update 7:303–313

    Article  CAS  PubMed  Google Scholar 

  6. Liu YZ, Liu YJ, Recker RR, Deng HW (2003) Molecular studies of identification of genes for osteoporosis: the 2002 update. J Endocrinol 177:147–196

    Article  CAS  PubMed  Google Scholar 

  7. Inoue M, Minami S, Nakata Y, Kitahara H, Otsuka Y, Isobe K, Takaso M, Tokunaga M, Nishikawa S, Maruta T, Moriya H (2002) Association between estrogen receptor gene polymorphisms and curve severity of idiopathic scoliosis. Spine (Phila Pa 1976) 27:2357–2362

    Article  Google Scholar 

  8. Wu J, Qiu Y, Zhang L, Sun Q, Qiu X, He Y (2006) Association of estrogen receptor gene polymorphisms with susceptibility to adolescent idiopathic scoliosis. Spine (Phila Pa 1976) 31:1131–1136

    Article  Google Scholar 

  9. Tang NL, Yeung HY, Lee KM, Hung VW, Cheung CS, Ng BK, Kwok R, Guo X, Qin L, Cheng JC (2006) A relook into the association of the estrogen receptor [alpha] gene (PvuII, XbaI) and adolescent idiopathic scoliosis: a study of 540 Chinese cases. Spine (Phila Pa 1976) 31:2463–2468

    Article  Google Scholar 

  10. Takahashi Y, Matsumoto M, Karasugi T, Watanabe K, Chiba K, Kawakami N, Tsuji T, Uno K, Suzuki T, Ito M, Sudo H, Minami S, Kotani T, Kono K, Yanagida H, Taneichi H, Takahashi A, Toyama Y, Ikegawa S (2011) Replication study of the association between adolescent idiopathic scoliosis and two estrogen receptor genes. J Orthop Res 29:834–837

    Article  CAS  PubMed  Google Scholar 

  11. Janusz P, Kotwicki T, Andrusiewicz M, Kotwicka M (2013) XbaI and PvuII polymorphisms of estrogen receptor 1 gene in females with idiopathic scoliosis: no association with occurrence or clinical form. PLoS ONE 8:e76806

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Bodmer W, Bonilla C (2008) Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet 40:695–701

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Database of Single Nucleotide Polymorphisms (dbSNP) (2013) Reference SNP (refSNP) Cluster Report: rs9340799 [build 138]. http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?rs=9340799. Accessed 2 Dec 2013

  14. Salanti G, Sanderson S, Higgins JP (2005) Obstacles and opportunities in meta-analysis of genetic association studies. Genet Med 7:13–20

    Article  PubMed  Google Scholar 

  15. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535

    Article  PubMed Central  PubMed  Google Scholar 

  16. Wells GA, Shea B, O’Connell D, Peterson J, Welch V, Losos M, Tugwell P (2013) 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 3 Dec 2013

  17. Little J, Higgins JPT, Eds: The HuGENet HuGE Review Handbook, version 1.0. http://www.med.uottawa.ca/public-health-genomics/web/assets/documents/HuGE_Review_Handbook_V1_0.pdf. Accessed 2 Dec 2013

  18. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed Central  PubMed  Google Scholar 

  19. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  20. Ioannidis JP, Trikalinos TA (2007) The appropriateness of asymmetry tests for publication bias in meta-analyses: a large survey. CMAJ 176:1091–1096

    Article  PubMed Central  PubMed  Google Scholar 

  21. Zhao D, Qiu GX, Wang YP, Zhang JG, Shen JX, Wu ZH (2009) Association between adolescent idiopathic scoliosis with double curve and polymorphisms of calmodulin1 gene/estrogen receptor-α gene. Orthop Surg 1:222–230

    Article  PubMed  Google Scholar 

  22. Little J, Higgins JP, Ioannidis JP, Moher D, Gagnon F, von Elm E, Khoury MJ, Cohen B, Davey-Smith G, Grimshaw J, Scheet P, Gwinn M, Williamson RE, Zou GY, Hutchings K, Johnson CY, Tait V, Wiens M, Golding J, van Duijn C, McLaughlin J, Paterson A, Wells G, Fortier I, Freedman M, Zecevic M, King R, Infante-Rivard C, Stewart A, Birkett N (2009) Strengthening the reporting of genetic association studies (STREGA): an extension of the STROBE Statement. Hum Genet 125:131–151

    Article  PubMed  Google Scholar 

  23. Salanti G, Amountza G, Ntzani EE, Ioannidis JP (2005) Hardy–Weinberg equilibrium in genetic association studies: an empirical evaluation of reporting, deviations, and power. Eur J Hum Genet 13:840–848

    Article  CAS  PubMed  Google Scholar 

  24. Xu J, Turner A, Little J, Bleecker ER, Meyers DA (2002) Positive results in association studies are associated with departure from Hardy–Weinberg equilibrium: hint for genotyping error? Hum Genet 111:573–574

    Article  PubMed  Google Scholar 

  25. Thomas DC, Witte JS (2002) Point: population stratification: a problem for case–control studies of candidate–gene associations? Cancer Epidemiol Biomarkers Prev 11:505–512

    PubMed  Google Scholar 

  26. Xu L, Qiu X, Sun X, Mao S, Liu Z, Qiao J, Qiu Y (2011) Potential genetic markers predicting the outcome of brace treatment in patients with adolescent idiopathic scoliosis. Eur Spine J 20:1757–1764

    Article  PubMed Central  PubMed  Google Scholar 

  27. Thanassoulis G, Vasan RS (2010) Genetic cardiovascular risk prediction: will we get there? Circulation 122:2323–2334

    Article  PubMed Central  PubMed  Google Scholar 

  28. Ogilvie J (2010) Adolescent idiopathic scoliosis and genetic testing. Curr Opin Pediatr 22:67–70

    Article  PubMed  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. The Ottawa Hospital, University of Ottawa Spine Program, 1053 Carling Avenue, Ottawa, ON, K1Y 4E9, Canada

    Suzan Chen, Darren M. Roffey, Philippe Phan & Eugene K. Wai

  2. Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA

    Linlu Zhao

  3. Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada

    Darren M. Roffey & Eugene K. Wai

  4. Division of Orthopaedic Surgery, University of Ottawa, Ottawa, ON, Canada

    Philippe Phan & Eugene K. Wai

Authors
  1. Suzan Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Linlu Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Darren M. Roffey
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Philippe Phan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eugene K. Wai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Suzan Chen.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, S., Zhao, L., Roffey, D.M. et al. Association between the ESR1 -351A>G single nucleotide polymorphism (rs9340799) and adolescent idiopathic scoliosis: a systematic review and meta-analysis. Eur Spine J 23, 2586–2593 (2014). https://doi.org/10.1007/s00586-014-3481-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00586-014-3481-x

Keywords

Search

Navigation