Skip to main content
SpringerLink
Log in

Genetic variation involved in the risk to external apical root resorption in orthodontic patients: a systematic review

  • Review
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objective

To perform a systematic review/meta-analysis to elucidate the scientific basis for the association between genetic variations and risk of external apical root resorption (EARR) in orthodontic patients.

Materials and methods

Four databases (PubMed, Web of Science, Scopus, LILACS) were electronically searched until November 22, 2020, followed by manual and gray literature search. Case-control or cross-sectional studies that evaluated genes involved in the susceptibility of orthodontic patients to EARR were eligible. Two reviewers applied the inclusion and exclusion criteria, extracted qualitative data, as well as assessed methodological quality using instrument proposed for genetic studies. For synthesis results, narrative and quantitative data (meta-analysis) were performed. The certainty of the evidence was tested using the GRADE Working Group approach.

Results

Of 201 articles in total, 16 studies were included in the review. Of these, 11 presented moderate and 5 of high methodological quality. In the narrative analysis, from 16 studies, 15 studies (10 genes) showed a significant association with EARR and 9 studies were included in the meta-analysis. Only the polymorphism rs208294 in P2RX7 (dominant model) was associated with EARR (OR = 0.52, 95%CI = 0.29–0.95, p = 0.03) and presented a very low certainty of the evidence.

Conclusion

Narrative analyses of individual studies demonstrated an association of many genes. The number of studies for each genetic variation was very low, and methodological heterogeneity between the studies was observed. Quantitative analyses (meta-analysis) could only show an involvement for P2RX7 (rs208294) in the risk of orthodontic patients to EARR at a very low certainty of evidence. (CRD42018085411).

Clinical relevance

The knowledge regarding the molecular aspects involved in the etiology of EARR will allow orthodontists to use a personalized treatment and early diagnosis of risk patients. This systematic review demonstrates that more studies are necessary to unravel the role of genetic variation for patients’ risk to EARR during orthodontic tooth movement.

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

Similar content being viewed by others

References

  1. Al-Qawasmi RA, Hartsfield JK Jr, Everett ET, Flury L, Liu L, Foroud TN, Macri JV, Roberts WE (2003) Genetic predisposition to external apical root resorption. Am J Orthod Dentofacia Orthop 123(3):242–252. https://doi.org/10.1067/mod.2003.42

    Article  Google Scholar 

  2. Al-Qawasmi RA, Hartsfield JK, Everett ET, Flury L, Liu L, Foroud TM, Macri JV, Roberts WE (2003) Genetic predisposition to external apical root resorption in orthodontic patients: linkage of chromosome-18 marker. J Dent Res 82(5):356–360. https://doi.org/10.1177/154405910308200506

    Article  PubMed  Google Scholar 

  3. Brezniak N, Wasserstein A (2002) Orthodontically induced inflammatory root resorption. Part I: the basic science aspects. Angle Orthod 72(2):180–184

    PubMed  Google Scholar 

  4. Linhartova P, Cernochova P, Izakovicova Holla L (2013) IL1 gene polymorphisms in relation to external apical root resorption concurrent with orthodontia. Oral Dis 19(3):262–270. https://doi.org/10.1111/j.1601-0825.2012.01973.x

    Article  PubMed  Google Scholar 

  5. Pereira S, Lavado N, Nogueira L, Lopez M, Abreu J, Silva H (2014) Polymorphisms of genes encoding P2X7R, IL-1B, OPG and RANK in orthodontic-induced apical root resorption. Oral Dis 20(7):659–667. https://doi.org/10.1111/odi.12185

    Article  PubMed  Google Scholar 

  6. Iglesias-Linares A, Yañez-Vico RM, Ballesta S, Ortiz-Ariza E, Mendoza-Mendoza A, Perea E, Solano-Reina E (2012) Interleukin 1 gene cluster SNPs (rs1800587, rs1143634) influences post-orthodontic root resorption in endodontic and their contralateral vital control teeth differently. Int Endod J 45(11):1018–1026. https://doi.org/10.1111/j.1365-2591.2012.02065.x

    Article  PubMed  Google Scholar 

  7. Iglesias-Linares A, Yañez-Vico RM, Ballesta-Mudarra S, Ortiz-Ariza E, Ortega-Rivera H, Mendoza-Mendoza A, Solano-Reina E, Perea-Pérez E (2012) Postorthodontic external root resorption is associated with IL1 receptor antagonist gene variations. Oral Dis 18(2):198–205. https://doi.org/10.1111/j.1601-0825.2011.01865.x

    Article  PubMed  Google Scholar 

  8. Gülden N, Eggermann T, Zerres K, Beer M, Meinelt A, Diedrich P (2009) Interleukin-1 polymorphisms in relation to external apical root resorption (EARR). J Orofac Orthop 70(1):20–38. https://doi.org/10.1007/s00056-009-8808-6

    Article  PubMed  Google Scholar 

  9. Lages EMB, Drummond AF, Pretti H, Costa FO, Lages EJ, Gontijo AI, Miranda Cota LO, Brito RB Jr (2009) Association of functional gene polymorphism IL-1beta in patients with external apical root resorption. Am J Orthod Dentofacial Orthop 136(4):542–546. https://doi.org/10.1016/j.ajodo.2007.10.051

    Article  PubMed  Google Scholar 

  10. Sharab LY, Morford LA, Dempsey J, Falcão-Alencar G, Mason A, Jacobson E, Kluemper GT, Macri JV, Hartsfield JK Jr (2015) Genetic and treatment-related risk factors associated with external apical root resorption (EARR) concurrent with orthodontia. Orthod Craniofac Res 18(Suppl l):71–82. https://doi.org/10.1111/ocr.12078

    Article  PubMed  PubMed Central  Google Scholar 

  11. Guo Y, He S, Gu T, Liu Y, Chen S (2016) Genetic and clinical risk factors of root resorption associated with orthodontic treatment. Am J Orthod Dentofacial Orthop 150(2):283–289. https://doi.org/10.1016/j.ajodo.2015.12.028

    Article  PubMed  Google Scholar 

  12. Pereira S, Nogueira L, Canova F, Lopez M, Silva HC (2016) IRAK1 variant is protective for orthodontic-induced external apical root resorption. Oral Dis 22(7):658–664. https://doi.org/10.1111/odi.12514

    Article  PubMed  Google Scholar 

  13. Borilova Linhartova P, Cernochova P, Kastovsky J, Vrankova Z, Sirotkova M, Izakovicova Holla L (2017) Genetic determinants and postorthodontic external apical root resorption in Czech children. Oral Dis 23(1):29–35. https://doi.org/10.1111/odi.12564

    Article  PubMed  Google Scholar 

  14. Castilhos BB, Souza CM, Simas Netta Fontana MLSSN, Pereira FA, Tanaka OM, Trevilatto PC (2019) Association of clinical variables and polymorphisms in RANKL, RANK, and OPG genes with external apical root resorption. Am J Orthod Dentofacial Orthop 155(4):529–542. https://doi.org/10.1016/j.ajodo.2018.05.016

    Article  Google Scholar 

  15. Wu FL, Wang LY, Huang YQ, Guo WB, Liu CD, Li SG (2013) Interleukin-1β +3954 polymorphisms and risk of external apical root resorption in orthodontic treatment: a meta-analysis. Genet Mol Res 12(4):4678–4686. https://doi.org/10.4238/2013.October.18.6

    Article  PubMed  Google Scholar 

  16. Aminoshariae A, Aminoshariae A, Valiathan M, Kulild JC (2016) Association of genetic polymorphism and external apical root resorption: a systematic review. Angle Orthod 86(6):1042–1049. https://doi.org/10.2319/011916-50.1

    Article  PubMed  Google Scholar 

  17. Nowrin SA, Jaafar S, Rahman NA, Basri R, Alam MK, Shahid F (2018) Association between genetic polymorphisms and external apical root resorption: a systematic review and meta-analysis. Korean J Orthod 48(6):395–404. https://doi.org/10.4041/kjod.2018.48.6.395

    Article  PubMed  PubMed Central  Google Scholar 

  18. Behnaz M, Mohammad-Rahimi H, Javaheri F, Omrani MD, Noroozi R, Taheri M, Ghafouri-Fard S (2020) The rs1143634 of IL-1β gene is associated with external apical root resorption in Iranian population. Meta Gene 24(6). https://doi.org/10.1016/j.mgene.2020.100711

  19. Iber-Díaz P, Senen-Carramolino R, Iglesias-Linares A, Fernández-Navarro P, Flores-Mir C, Yañez-Vico RM (2020) GWAS of Post-orthodontic aggressive external apical root resorption identified multiple putative loci at X-Y chromosomes. J Pers Med 10(4):169. https://doi.org/10.3390/jpm10040169

    Article  PubMed Central  Google Scholar 

  20. Higgins J, Thomas J, Chandler J et al (2019) Cochrane handbook for systematic reviews of interventions, 2nd edn. John Wiley & Sons, Chichester (UK)

    Book  Google Scholar 

  21. Garner P, Hopewell S, Chandler J, MacLehose H, Schünemann HJ, Akl EA, Beyene J, Chang S, Churchill R, Dearness K, Guyatt G, Lefebvre C, Liles B, Marshall R, Martínez García L, Mavergames C, Nasser M, Qaseem A, Sampson M, Soares-Weiser K, Takwoingi Y, Thabane L, Trivella M, Tugwell P, Welsh E, Wilson EC, Schünemann HJ, Panel for updating guidance for systematic reviews (PUGs) (2016) When and how to update systematic reviews: consensus and checklist. BMJ 354:i3507. https://doi.org/10.1136/bmj.i3507

    Article  PubMed  PubMed Central  Google Scholar 

  22. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD et al (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 372:n71

    Article  Google Scholar 

  23. Clark MF, Baudouin SV (2006) A systematic review of the quality of genetic association studies in human sepsis. Intensive Care Med 32(11):1706–12. https://doi.org/10.1007/s00134-006-0327-y

    Article  PubMed  Google Scholar 

  24. Borenstein et al (2009) Introduction to meta-analysis. John Wiley and Sons Ltd, Chichester

    Book  Google Scholar 

  25. Song EAJ, Gilbody S, Duley L, Sutton AJ (2000) Publication and related biases. Health Technol Assess 4:1–115

    PubMed  Google Scholar 

  26. Schünemann H, Brożek J, Guyatt G, Oxman A (2013) GRADE handbook for grading quality of evidence and strength of recommendations. The GRADE Working Group. Available from: www.guidelinedevelopment.org/handbook

  27. Tomoyasu Y, Yamaguchi T, Tajima A, Inoue I, Maki K (2009) External apical root resorption and the interleukin-1B gene polymorphism in the Japanese population. Orthod Waves 68(4):152–157. https://doi.org/10.1016/j.odw.2009.05.002

    Article  Google Scholar 

  28. Fontana ML, de Souza CM, Bernardino JF, Hoette F, Hoette ML, Thum L, Ozawa TO, Capelozza Filho L, Olandoski M, Trevilatto PC (2012) Association analysis of clinical aspects and vitamin D receptor gene polymorphism with external apical root resorption in orthodontic patients. Am J Orthod Dentofacial Orthop 142(3):339–47. https://doi.org/10.1016/j.ajodo.2012.04.013

    Article  PubMed  Google Scholar 

  29. Iglesias-Linares A, Yañez-Vico RM, Moreno-Fernández AM, Mendoza-Mendoza A, Orce-Romero A, Solano-Reina E (2014) Osteopontin gene SNPs (rs9138, rs11730582) mediate susceptibility to external root resorption in orthodontic patients. Oral Dis 20(3):307–312. https://doi.org/10.1111/odi.12114

    Article  PubMed  Google Scholar 

  30. Harris EF, Kineret SE, Tolley EA (1997) A heritable component for external apical root resorption in patients treated orthodontically. Am J Orthod Dentofacial Orthop 111(3):301–309. https://doi.org/10.1016/s0889-5406(97)70189-6

    Article  PubMed  Google Scholar 

  31. Linge BO, Linge L (1983) Apical root resorption in upper anterior teeth. Eur J Orthod 5:173–183. https://doi.org/10.1093/ejo/5.3.173

    Article  PubMed  Google Scholar 

  32. Linge L, Linge BO (1991) Patient characteristics and treatment variables associated with apical root resorption during orthodontic treatment. Am J Orthod Dentofacial Orthop 99:35–43. https://doi.org/10.1016/S0889-5406(05)81678-6

    Article  PubMed  Google Scholar 

  33. Brezniak N, Goren S, Zoizner R, Dinbar A, Arad A, Wasserstein A, Heller M (2004) A comparison of three methods to accurately measure root length. Angle Orthod 74:786–791. https://doi.org/10.1043/0003-3219(2004)074<0786:ACOTMT>2.0.CO;2

  34. Küchler EC, Schröder A, Corso P, Scariot R, Spanier G, Proff P, Kirschneck C (2019) Genetic polymorphisms influence gene expression of human periodontal ligament fibroblasts in the early phases of orthodontic tooth movement. Odontology 108:493–502. https://doi.org/10.1007/s10266-019-00475-x

    Article  PubMed  Google Scholar 

  35. Rock KL, Kono H (2008) The inflammatory response to cell death. Annu Rev Pathol 3:99–126. https://doi.org/10.1146/annurev.pathmechdis.3.121806.151456

    Article  PubMed  PubMed Central  Google Scholar 

  36. Kapoor P, Kharbanda OP, Monga N, Miglani R, Kapila S (2014) Effect of orthodontic forces on cytokine and receptor levels in gingival crevicular fluid: a systematic review. Prog Orthod 15(1):65. https://doi.org/10.1186/s40510-014-0065-6

    Article  PubMed  PubMed Central  Google Scholar 

  37. Abbasian MH, Abbasi B, Ansarinejad N, Ardekani AM, Samizadeh E, Moghaddam KG, Hashemi MR (2018) Association of interleukin-1 gene polymorphism with risk of gastric and colorectal cancers in an Iranian population. Iran J Immuno 15(4):321–8. https://doi.org/10.22034/IJI.2018.39401

    Article  Google Scholar 

  38. Chung CJ, Soma K, Rittling SR, Denhardt DT, Hayata T, Nakashima K, Ezura Y, Noda M (2008) OPN deficiency suppresses appearance of odontoclastic cells and resorption of the tooth root induced by experimental force application. J Cell Physiol 214:614–620. https://doi.org/10.1002/jcp.21250

    Article  PubMed  Google Scholar 

  39. Ishida R, Emi M, Ezura Y, Iwasaki H, Yoshida H, Suzuki T, Hosoi T, Inoue S, Shiraki M, Ito H, Orimo H (2003) Association of a haplotype (196Phe/532Ser) in the interleukin-1-receptor-associated kinase (IRAK1) gene with low radial bone mineral density in two independent populations. J Bone Miner Res 18:419–423. https://doi.org/10.1359/jbmr.2003.18.3.419

    Article  PubMed  Google Scholar 

  40. Arcaroli J, Silva E, Maloney JP, He Q, Svetkauskaite D, Murphy JR, Abraham E (2006) Variant IRAK-1 haplotype is associated with increased nuclear factor-kappaB activation and worse outcomes in sepsis. Am J Respir Crit Care Med 173:1335–1341. https://doi.org/10.1164/rccm.200603-341OC

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This systematic review and meta-analysis study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance Code 001 and by the Alexander von Humboldt Foundation (Küchler/Kirschneck accepted on July 4, 2019).

Author information

Authors and Affiliations

  1. Postgraduate Program in Dentistry of Niterói, Faculty of Dentistry, Federal Fluminense University, Niterói, Rio de Janeiro, Brazil

    Liz Helena Moraes Pinheiro, Ludmila Silva Guimarães, Leonardo Santos Antunes & Lívia Azeredo Alves Antunes

  2. Postgraduate Program in Dentistry, Department of Specific Formation, School of Dentistry, Health Institute of Nova Friburgo, Fluminense Federal University, Nova Friburgo, RJ, Brazil

    Leonardo Santos Antunes & Lívia Azeredo Alves Antunes

  3. Department of Orthodontics, University Medical Centre of Regensburg, Franz-Josef-Strauss-Allee 11, 93053, Regensburg, Germany

    Erika Calvano Küchler & Christian Kirschneck

  4. Department of Specific Formation, School of Dentistry, Fluminense Federal University, St. Doutor Silvio Henrique Braune 22, Centro - Nova Friburgo, 28625-650, Rio de Janeiro, Brazil

    Lívia Azeredo Alves Antunes

Authors
  1. Liz Helena Moraes Pinheiro
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ludmila Silva Guimarães
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leonardo Santos Antunes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Erika Calvano Küchler
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christian Kirschneck
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lívia Azeredo Alves Antunes
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Data collection and analysis were performed by Liz Helena Moraes Pinheiro, Lívia Azeredo Alves Antunes, Ludmila Silva Guimarães, and Leonardo Santos Antunes. The first draft of the manuscript was written by Liz Helena Moraes Pinheiro and Lívia Azeredo Alves Antunes. The final draft was written and revised by Lívia Azeredo Alves Antunes (systematic review methods), Erika Calvano Küchler (genetic polymorphisms), and Christian Kirschneck (orthodontics), and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Lívia Azeredo Alves Antunes.

Ethics declarations

Ethics approval

Not applicable.

Informed consent

Not applicable.

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pinheiro, L.H.M., Guimarães, L.S., Antunes, L.S. et al. Genetic variation involved in the risk to external apical root resorption in orthodontic patients: a systematic review. Clin Oral Invest 25, 5613–5627 (2021). https://doi.org/10.1007/s00784-021-04074-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-021-04074-5

Keywords

Search

Navigation