External Apical Root Resorption and IL-1A, IL-1RN Gene Polymorphisms: A Systematic Review and Meta-Analysis of Prospective Studies


  • Shifat A. Nowrin
  • Saidi Jaafar
  • Norma Ab Rahman
  • Fazal Shahid
  • Rehana Basri
  • Mohammad Khursheed Alam


Polymorphism, Genetic, Root Resorption, Orthodontics, Study Characteristics


Objective: To reconnoiter the IL-1A (-889) and IL-1RN (+2018) gene polymorphisms and their association with EARR. Material and Methods: The Science Direct, PubMed and Scopus databases were comprehensively searched by two independent reviewers. In addition, the bibliographies of all relevant publications and textbooks were searched manually. A meta-analysis was performed using data available up to May 9, 2020. Results: A total of 13 and 9 publications were selected for the systematic review and meta-analysis, respectively for both IL-1A and IL-1RN genes. Odds ratio (OR) was used to evaluate the association of the gene polymorphism and the risk of EARR. The risk of EARR was estimated using the overall OR from the published studies. No association was found for IL-1A gene for the risk of EARR. However, the dominant and co-dominant models of IL-1RN gene polymorphism were associated with the risk of EARR. Conclusion: More studies are warranted to determine the relationship between IL-1A and IL-1RN gene polymorphisms and EARR for a clearer understanding of their interactions.


Al-Qawasmi RA, Hartsfield JK Jr., Everett ET, Flury L, Liu L, Foroud TM, et al. Genetic predisposition to external apical root resorption. Am J Orthod Dentofacial Orthop 2003; 123(3):242-52. https://doi.org/10.1067/mod.2003.42

Iglesias-Linares A, Yanez-Vico R, Ballesta-Mudarra S, Ortiz-Ariza E, Ortega-Rivera H, Mendoza-Mendoza A, et al. Postorthodontic external root resorption is associated with IL1 receptor antagonist gene variations. Oral Dis 2012; 18(2):198-205. https://doi.org/10.1111/j.1601-0825.2011.01865.x

Linhartova P, Cernochova P, Holla LI. IL1 gene polymorphisms in relation to external apical root resorption concurrent with orthodontia. Oral Dis 2013; 19(3):262-70. https://doi.org/10.1111/j.1601-0825.2012.01973.x

Tomoyasu Y, Yamaguchi T, Tajima A, Inoue I, Maki K. External apical root resorption and the interleukin-1B gene polymorphism in the Japanese population. Orthodontic Waves 2009; 68(4):152-7. https://doi.org/10.1016/j.odw.2009.05.002

Vijayalakshmi R, Geetha A, Ramakrishnan T, Emmadi P. Genetic polymorphisms in periodontal diseases: an overview. Indian J Dent Res 2010; 21(4):568-74. https://doi.org/10.4103/0970-9290.74226

Dunn E, Sims JE, Nicklin MJ, O'Neill LA. Annotating genes with potential roles in the immune system: six new members of the IL-1 family. Trends Immunol 2001; 22(10):533-6. https://doi.org/10.1016/s1471-4906(01)02034-8

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

Iglesias-Linares A, Yanez-Vico RM, Ballesta-Mudarra S, Ortiz-Ariza E, Mendoza-Mendoza A, Perea-Perez E, et al. Interleukin 1 receptor antagonist (IL1RN) genetic variations condition post-orthodontic external root resorption in endodontically-treated teeth. Histol Histopathol 2013; 28(6):767-73. https://doi.org/10.14670/HH-28.767

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

Pereira S, Lavado N, Nogueira L, Lopez M, Abreu J, Silva H. Polymorphisms of genes encoding P2X7R, IL-1B, OPG and RANK in orthodontic-induced apical root resorption. Oral Dis 2014; 20(7):659-67. https://doi.org/10.1111/odi.12185

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

Wu FL, Wang LY, Huang YQ, Guo WB, Liu CD, Li SG. Interleukin-1β +3954 polymorphisms and risk of external apical root resorption in orthodontic treatment: A meta-analysis. Genet Mol Res 2013; 12(4):4678-86. https://doi.org/10.4238/2013.October.18.6

Landis JR, Koch GG. The measurement of observer agreement for categorical data. Biometrics 1977; 33(1):159-74.

Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 199; 50(4):1088-101.

Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315(7109):629-34. https://doi.org/10.1136/bmj.315.7109.629

Iglesias‐Linares A, Yañez‐Vico R, Ballesta S, Ortiz‐Ariza E, Mendoza‐Mendoza A, Perea E, et al. Interleukin 1 gene cluster SNPs (rs1800587, rs1143634) influences post‐orthodontic root resorption in endodontic and their contralateral vital control teeth differently. Int Endod J 2012; 45(11):1018-26.

Iglesias-Linares A, Yañez-Vico R-M, Ortiz-Ariza E, Ballesta S, Mendoza-Mendoza A, Perea E, et al. Postorthodontic external root resorption in root-filled teeth is influenced by interleukin-1β polymorphism. J Endod 2012; 38(3):283-87.

Sharab L, Morford L, Dempsey J, Falcão-Alencar G, Mason A, Jacobson E, et al. Genetic and treatment-related risk factors associated with external apical root resorption (EARR) concurrent with orthodontia. Orthod Craniofac Res 2015; 18(suppl 1):71-82. https://doi.org/10.1111/ocr.12078

Guo Y, He S, Gu T, Liu Y, Chen S. Genetic and clinical risk factors of root resorption associated with orthodontic treatment. Am J Orthod Dentofacial Orthop 2016; 150(2):283-89. https://doi.org/10.1016/j.ajodo.2015.12.028.

Aminoshariae A, Aminoshariae A, Valiathan M, Kulild JC. Association of genetic polymorphism and external apical root resorption. Angle Orthod 2016; 86(6):1042-9. https://doi.org/10.2319/011916-50.1

Pereira S, Nogueira L, Canova F, Lopez M, Silva H. IRAK 1 variant is protective for orthodontic-induced external apical root resorption. Oral dis 2016; 22(7), 658-64. https://doi.org/10.1111/odi.12514

Roodman GD. Role of cytokines in the regulation of bone resorption. Calcif Tissue Int 1993; 53(suppl 1):S94-98. https://doi.org/10.1007/BF01673412

Gowen M, Wood DD, Ihrie EJ, McGuire MK, Russell RGG. An interleukin 1 like factor stimulates bone resorption in vitro. Nature 1983; 306(5941):378-80. https://doi.org/10.1038/306378a0

Salla JT, de Albuquerque Taddei SR, Queiroz-Junior CM, Junior IA, Teixeira MM, Silva TA. The effect of IL-1 receptor antagonist on orthodontic tooth movement in mice. Arch Oral Biol 2012; 57(5):519-24. https://doi.org/10.1016/j.archoralbio.2011.09.018




How to Cite

Nowrin, S. A. ., Jaafar, S. ., Rahman, N. A. ., Shahid, F. ., Basri, R. ., & Alam, M. K. . (2021). External Apical Root Resorption and IL-1A, IL-1RN Gene Polymorphisms: A Systematic Review and Meta-Analysis of Prospective Studies. Pesquisa Brasileira Em Odontopediatria E Clínica Integrada, 21, e0217. Retrieved from https://revista.uepb.edu.br/PBOCI/article/view/685



Systematic Reviews (and Meta-Analysis)