PINHEIRO, Liz Helena Moraes; MOURA, Dalila Ferreira Silvano de; ANTUNES, Leonardo Santos; ANTUNES, Lívia Azeredo Alves

Liz Helena Moraes PINHEIRO

Conception or design of the study

Data acquisition, analysis or interpretation

Writing the article

Critical revision of the article

Final approval of the article

Overall responsibility

Fluminense Federal University, Postgraduate Program in Dentistry (Niterói/RJ, Brazil).

https://orcid.org/0000-0001-5503-5794

Dalila Ferreira Silvano de MOURA

Data acquisition, analysis or interpretation

Writing the article

Critical revision of the article

Final approval of the article

Overall responsibility

Fluminense Federal University, Nova Friburgo Institute of Health, School of Biomedicine (Nova Friburgo/RJ, Brazil).

https://orcid.org/0009-0008-8047-974X

Leonardo Santos ANTUNES

Conception or design of the study

Data acquisition, analysis or interpretation

Critical revision of the article

Final approval of the article

Overall responsibility

Fluminense Federal University, Postgraduate Program in Dentistry (Niterói/RJ, Brazil).

Fluminense Federal University, Nova Friburgo Institute of Health, Department of Specific Formation (Nova Friburgo/RJ, Brazil).

https://orcid.org/0000-0002-2115-6958

Lívia Azeredo Alves ANTUNES

Data acquisition, analysis or interpretation

Critical revision of the article

Final approval of the article

Overall responsibility

Fluminense Federal University, Nova Friburgo Institute of Health, Department of Specific Formation (Nova Friburgo/RJ, Brazil).

https://orcid.org/0000-0002-8432-0815

liviaazeredo@gmail.com

»
The authors report no commercial, proprietary or financial interest in the products or companies described in this article.

Authors/Year/ Area of dental research	Genes (SNP) evaluated	Polymorphism Association with EARR
Authors/Year/ Area of dental research	Genes (SNP) evaluated	Yes	No
*Sharab et al.²2 Sharab LY, Morford LA, 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 Apr;18(Suppl 1):71-82. (2015) Orthodontics	P2RX7 (rs208294, rs1718119, rs2230912) CASP1/ICE (rs580253, rs554344, rs530537 IL1-B (rs1143634) IL1-A (rs1800587) IL1RA (rs41959)	P2RX7 (rs208294)	P2RX7 (rs1718119, rs2230912) CASP1/ICE (rs580253, rs554344, rs530537 IL1-B (rs1143634) IL1-A (rs1800587) IL1RA (rs41959)
*Al-Qawasmi et al.⁵5 Al-Qawasmi RA, Hartsfield JK, Everett ET, Flury L, Liu L, Foroud TM, et al. Genetic predisposition to external apical root resorption. Am J Orthod Dentofacial Orthop. 2003 Mar;123(3):242-52. (2003) Orthodontics	IL1-A (rs1143634) IL1-B (rs1143627)	IL1-B (rs1143627)	IL1-A (rs1143634)
*Bastos Lages et al.⁶6 Bastos Lages EM, Drummond AF, Pretti H, Costa FO, Lages EJP, Gontijo AI, et al. Association of functional gene polymorphism IL-1beta in patients with external apical root resorption. Am J Orthod Dentofacial Orthop. 2009 Oct;136(4):542-6. (2009) Orthodontics	IL-1B (rs1143634)	IL-1B (rs1143634)	______
*Linhartova et al.⁷7 Linhartova P, Cernochova P, Izakovicova Holla L. IL1 gene polymorphisms in relation to external apical root resorption concurrent with orthodontia. Oral Dis. 2013 Apr;19(3):262-70. (2013) Orthodontics	IL1A (rs16347) IL1B (rs1143627) IL1RN (rs9005)	IL1A (rs16347) IL1B (rs1143627) IL1RN (rs9005)/Short alleles	IL1B (rs1143627) IL1RN (rs9005)/Long alleles
*Iglesias-Linares et al.⁸8 Iglesias-Linares A, Yañez-Vico RM, 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 Nov;45(11):1018-26. (2012) Endodontics	IL1A(rs1800587) IL1B (rs1143634)	IL1B (rs1143634)	IL1 (rs1800587)
*Guo et al.⁹9 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 Aug;150(2):283-9. (2016) Orthodontics	IL-6 (rs1800796) IL1RN (rs419598)	IL-6 (rs1800796)	IL1RN (rs419598)
Borges de Castilhos et al.¹⁰10 Castilhos BB, Souza CM, Fontana MLS, Pereira FA, Tanaka OM, Trevilatto PC. Association of clinical variables and polymorphisms in RANKL, RANK, and OPG genes with external apical root resorption. Am J Orthod Dentofacial Orthop. 2019 Apr;155(4):529-42. (2019) Orthodontics	RANKL (rs1038434, rs3742257, rs931273, rs12585229) RANK (rs12455775) OPG (rs2875845, rs3102724, rs1032128, rs3102728)	RANK (rs12455775) OPG (rs2875845, rs3102724, rs1032128, rs3102728)	RANKL (rs1038434, rs3742257, rs931273, rs12585229)
*Iglesias-Linares et al.¹²12 Iglesias-Linares A, Yañez-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 Mar;18(2):198-205. (2012) Orthodontics	IL1A (rs1800587) IL1B (rs1143634) IL1RN (rs419598)	IL1B (rs1143634) IL1RN (rs419598)	IL1A (rs1800587)
*Tomoyasu et al.¹⁷17 Tomoyasu Y, Yamaguchi T, Tajima A, Inoue I, Maki K. External apical root resorption and the interleukin-1B gene polymorphism in the Japanese population. Orthod Waves. 2009 Dec;68(4):152-7. (2009) Orthodontics	IL-1B (rs1143634)	______	IL-1B (rs1143634)
*Pereira et al.¹⁸18 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 Oct;20(7):659-67. (2014) Orthodontics	OPG (rs3102735) RANK (rs1805034) IL-1B (rs1143634) P2RX7 (rs1718119)	P2RX7 (rs1718119)	OPG (rs3102735) RANK (rs1805034) IL-1B (rs1143634)
*Borilova Linhartova et al.¹⁹19 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 Jan;23(1):29-35. (2017) Orthodontics	IL17A (rs2275913) P2RX7 (rs208294, rs1718119) SSP 1(rs9138, rs11730582) OPG (rs2073618, rs3102735)	P2RX7 (rs208294, rs1718119)	PPS 1 (rs9138, rs11730582) OPG (rs2073618, rs3102735)
*Fontana et al.²⁰20 Fontana MLSSN, Souza CM, Bernardino JF, Hoette F, Hoette ML, Thum L, et al. Association analysis of clinical aspects and vitamin D receptor gene polymorphism with external apical root resorption in orthodontic patients. Am J Orthod Dentofacial Orthop. 2012 Sep;142(3):339-47. (2012) Orthodontics	Vitamin D receptor TaqI	Vitamin D receptor TaqI	______
*Iglesias-Linares et al.²¹21 Iglesias-Linares A, Yañez-Vico RM, Moreno-Fernández AM, Mendoza-Mendoza A, Orce-Romero A, Solano-Reina E. Osteopontin gene SNPs (rs9138, rs11730582) mediate susceptibility to external root resorption in orthodontic patients. Oral Dis. 2014 Apr;20(3):307-12. (2014) Orthodontics	OPG (rs9138, rs11730582)	OPG (rs9138, rs11730582)	______
Urban and Mincik²²22 Urban D, Mincik J. Monozygotic twins with idiopathic internal root resorption: A case report. Aust Endod J. 2010 Aug;36(2):79-82. (2010) Endodontics	IL-1A IL-1B IL1RN	IL-1B	IL-1A IL1RN
**Lee et al.²⁵25 Lee YJ, Pak H, Hwang CJ, Choi YJ, Lee JH, Lee JH, et al. Targeted next-generation sequencing for comprehensive genetic analysis of external apical root resorption during orthodontic treatment with premolar extraction in the Korean population. Am J Orthod Dentofacial Orthop. 2022 Nov;162(5):668-679.e5. (2022) Orthodontics	SPP1 (rs 4754, rs1126616, rs9138) SFRP2 (rs3810765)	SPP1 (rs9138) SFRP2 (rs3810765)	SPP1 (rs 4754,rs1126616)
*Rutsch et al.²⁶26 Rutsch F, MacDougall M, Lu C, Buers I, Mamaeva O, Nitschke Y, et al. A specific IFIH1 gain-of-function mutation causes Singleton-Merten syndrome. Am J Hum Genet. 2015 Feb;96(2):275-82. (2015) other areas of dental research	MDA5 IFIH1	MDA5 IFIH1	______
*Al-Qawasmi et al.²⁷27 Al-Qawasmi RA, Hartsfield JK, Everett ET, Flury L, Liu L, Foroud TM, et al. Genetic predisposition to external apical root resorption in orthodontic patients: linkage of chromosome-18 marker. J Dent Res. 2003 May;82(5):356-60. (2003) Orthodontics	RANK (rs1805034) TNSALP (rs1256328) TNF-a (rs1799724)	RANK (rs1805034)	TNF-a (rs1799724) TNSALP (rs1256328)
*Gülden et al.²⁸28 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 Jan;70(1):20-38. (2009) Orthodontics	IL1-A (-889) IL1-B (+3954) (rs1143634)	IL1-A (-889) IL1-B (+3954)	IL-1B (rs1143634)
*Iglesias-Linares et al.²⁹29 Iglesias-Linares A, Sonnenberg B, Solano B, Yañez-Vico RM, Solano E, Lindauer SJ, et al. Orthodontically induced external apical root resorption in patients treated with fixed appliances vs removable aligners. Angle Orthod. 2017 Jan;87(1):3-10. (2017) Orthodontics	IL1-B (rs1143634) IL1RN (rs419598) SPP1 (rs9138, rs11730582)	IL1RN (rs419598)	IL1B (rs1143634) SPP1 (rs9138, rs11730582)
*Pettersson et al.³⁰30 Pettersson M, Bergendal B, Norderyd J, Nilsson D, Anderlid BM, Nordgren A, et al. Further evidence for specific IFIH1 mutation as a cause of Singleton-Merten syndrome with phenotypic heterogeneity. Am J Med Genet A. 2017 May;173(5):1396-9. (2017) Other areas of dental research	MDA5 IFIH1	MDA5 IFIH1	______
Pereira et al.³¹31 Pereira S, Nogueira L, Canova F, Lopez M, Silva HC. IRAK1 variant is protective for orthodontic-induced external apical root resorption. Oral Dis. 2016 Oct;22(7):658-64. (2016) Orthodontics	IL1B (rs1143634) IL1RN (rs315952) IRAK1 (rs1059703)	IRAK1 (rs1059703)	IL1B (rs1143634) IL1RN (rs315952)
Bastos et al.³²32 Bastos JV, Côrtes MIS, Silva JFC, Goulart EMA, Colosimo EA, Gomez RS, et al. A study of the interleukin-1 gene cluster polymorphisms and inflammatory external root resorption in replanted permanent teeth. Int Endod J. 2015 Sep;48(9):878-87. (2015) Other areas of dental research	IL1A (rs 180058) IL1B (rs1143634) IL1RN (rs419598)	______	IL1A (rs 180058) IL1B (rs1143634) IL1RN (rs419598)
Ciurla et al.³³33 Ciurla A, Marruganti C, Doldo T, Szymanska J. Association between polymorphisms in the IL-1ß, TNFRSF11B, CASP1, and IL-6 genes and orthodontic-induced external apical root resorption. J Clin Med. 2021 Sep;10(18):4166. (2021) Orthodontics	IL-1B (rs1143634) TNFRSF11B (rs3102735) CASP1(rs530537) IL-6 (rs1800796)	IL-1B (rs1143634)	TNFRSF11B (rs3102735) CASP1(rs530537) IL-6 (rs1800796)
Roskamp et al.³⁴34 Roskamp L, Trevilatto PC, Souza CM, Silva Neto UX, Carneiro E, Fariniuk LF, et al. Types of external root resorption of replanted teeth: analysis of the clinical aspects and of interleukin-4 gene polymorphisms involvement. J Endod. 2017 Nov;43(11):1792-6. (2017) Endodontics	IL4 (rs2227284, rs2243268)	______	IL4 (rs2227284, rs2243268)
Roskamp et al.³⁵35 Roskamp L, Trevilatto PC, Souza CM, Silva Neto UX, Carneiro E, Fariniuk LF, et al. Analysis of the association of clinical factors and IL4 gene polymorphisms with root resorption in avulsed teeth after 1 year of replantation. Int Endod J. 2018 Jan;51(1):12-9. (2018) Endodontics	IL4 (rs2227284, rs2243268)	______	IL4(rs2227284, rs2243268)
Behnaz et al.³⁶36 Behnaz M, Mohammad-Rahimi H, Javaheri F, Omrani MD, Noroozi R, Taheri M, et al. The rs1143634 of IL-1ß gene is associated with external apical root resorption in Iranian population. Meta Gene. 2020 Jun;24:100711. (2020) Orthodontics	IL-1A (rs1800587) IL-1B (rs1143634)	IL-1B (rs1143634)	IL-1A (rs1800587)
Ciurla et al.³⁷37 Ciurla A, Szymanska J, Plachno BJ, Bogucka-Kocka A. Polymorphisms of encoding genes IL1RN and P2RX7 in apical root resorption in patients after orthodontic treatment. Int J Mol Sci. 2021 Jan;22(2):777. (2021) Orthodontics	P2RX7 (rs208294) IL1RN (rs419598)	P2RX7 (rs208294) IL1RN (rs419598)	______
Iber-díaz et al.³⁸38 Iber-Díaz P, Senen-Carramolino R, Iglesias-Linares A, Fernández-Navarro P, Flores-Mir C, Yañez-Vico RM. GWAS of post-orthodontic aggressive external apical root resorption identified multiple putative loci at X-Y chromosomes. J Pers Med. 2020 Oct;10(4):169. (2020) Orthodontics	Multiple putative loci and genes located at somatic chromosomes 2, 4, 8, 12, 18, and at sexual chromosomes X and Y	STAG (rs151184635) RP1-30E17.2 (rs55839915) SSP1 (rs11730582) P2RX7 (rs1718119) TNFRSF11A (rs8086340)	Other loci and genes located on somatic chromosomes 2, 4, 8, 12, 18 and on sex chromosomes X and Y analyzed
Roskamp et al.³⁹39 Roskamp L, Trevilatto PC, Souza CM, Ignácio SA, Lima GD, Pereira TM, et al. The role of polymorphism of the IL6 gene in tooth replantation. Aust Endod J. 2021 Aug;47(2):314-9. (2021) Other areas of dental research	IL-6 (rs2069843)	IL-6 (rs2069843)	______
Bahirrah et al.⁴⁰40 Bahirrah S, Lestari W, Zulhakim A, Suwandi A, Irfanita N. External root resorption (EARR) and interleukin-1ß (rs1143634) gene polymorphism in the Bataknese population: a pilot study. AIP Conf Proc. 2023 Feb;2682(1):050007. (2023) Orthodontics	IL-IB (rs1143634)	______	IL-IB (rs1143634)
Marañón‐Vásquez et al.⁴¹41 Marañón-Vásquez G, Küchler EC, Hermann S, Paddenberg E, Schröder A, Baratto-Filho F, et al. Association between genetic variants in key vitamin-D-pathway genes and external apical root resorption linked to orthodontic treatment. Eur J Oral Sci. 2023 Apr;131(2):e12916. (2023) Orthodontics	VDR (rs1544410, rs7975232, rs731236, rs2228570) GC (rs4588) P450CYP27B1 (rs4646536) P450 CYP24A1(rs921650)	VDR (rs2228570) P450 CYP27B1 (rs4646536) P450 CYP24A1- less expressive	VDR (rs1544410, rs7975232, rs731236) GC (rs4588)
Silva et al.⁴²42 Silva HC, Lavado N, Canova F, Lopez MG, Regateiro FJ, Pereira SA. Influence of clinical factors on the protective or deleterious impact of genetic variants in orthodontically induced external root resorption: an observational study. BMC Oral Health. 2022 Jul;22(1):270. (2022) Orthodontics	TNFRSF11B gene, OPG (rs3102735) TNFRSF11A gene, RANK (rs1805034) IL-IB (rs1143634) P2RX7 (rs1718119) IL1RN (rs315952)	TNFRSF11B gene, OPG (rs3102735) P2RX7 (rs1718119) IL1RN (rs315952)	TNFRSF11A gene, encoding RANK (rs1805034) IL-IB (rs1143634)
Roskamp et al.⁴³43 Roskamp L, Souza CM, Ignácio SA, Perin CP, Mattos NHR, Sunye IR, et al. Influence of clinical factors, IL4 and IL6 genes polymorphisms in functional healing in late replantation. Braz Dent J. 2022;33(1):13-21. (2022) Other areas of dental research	IL4(rs2227284/rs2243268) IL6(rs1524107/rs2069835/rs2069838/rs2069840/rs2069843/rs2069845)	______	IL4(rs2243268)
Baghaei et al.⁴⁴44 Baghaei NN, Zhai G, Lamani E. Genetic and other factors contributing to external apical root resorption in orthodontic patients. Orthod Craniofac Res. 2023 Dec;26(Suppl 1):64-72. (2023) Orthodontics	IL-1A (rs1800587) IL-1B (rs1143634) \ IL-1RN (rs419598) P2RX7 (rs1718119, rs2230912 IRAK1 (rs1059703) CASP1 (rs530537, rs580253, rs554344)	IL-1A (rs1800587)	IL-1B (rs1143634) IL-1RN (rs419598) P2RX7 (rs1718119, rs2230912), IRAK1 (rs1059703) CASP1 (rs530537, rs580253, rs554344)
*Iglesias-Linares et al.⁴⁷47 Iglesias-Linares A, Yañez-Vico RM, Ortiz-Ariza E, Ballesta S, Mendoza-Mendoza A, Perea E, et al. Postorthodontic external root resorption in root-filled teeth is influenced by interleukin-1ß polymorphism. J Endod. 2012 Mar;38(3):283-748. (2012) Endodontics and Orthodontics	IL1A(rs1800587) IL1B (rs1143634)	IL1B (rs1143634)	IL1A (rs1800587)
Iglesias-Linares et al.⁴⁸48 Iglesias-Linares A, Yañez-Vico RM, Ballesta-Mudarra S, Ortiz-Ariza E, Mendoza-Mendoza A, Perea-Pérez E, et al. Interleukin 1 receptor antagonist (IL1RN) genetic variations condition post-orthodontic external root resorption in endodontically-treated teeth. Histol Histopathol. 2013 Jun;28(6):767-73. (2013) Endodontics and Orthodontics	IL1RN (rs419598)	IL1RN (rs419598)	_____
*Iglesias-Linares et al.⁴⁹49 Iglesias-Linares A, Morford LA, Hartsfield JK Jr. Bone density and dental external apical root resorption. Curr Osteoporos Rep. 2016 Dec;14(6):292-309. (2016) Other areas of dental research	IL-1B (rs1143634) IL1A (rs1800587) IL1RN (rs419598) IL-6 (rs1800796) P2RX7 (rs208294, rs1718119, rs2230912) TNFRSF11B (OPG) TNFRSF11A (rs3102735, rs1805034) RANKL (rs228769)	IL-1B (rs1143634) IL1A (rs1800587) P2RX7 (rs208294) TNFRSF11B (OPG) TNFRSF11A (rs3102735, rs1805034) RANKL (rs228769)	IL1RN (rs419598) P2RX7 (rs1718119, rs2230912)

Author/ year	Population	Sample (n) and study design	Age in years Mean (SD)	Orthodontic technique	Methods used to detect EARR	Imaging exams	Evaluated tooth/teeth	Angle malocclusion
Al-Qawasmi et al.⁵5 Al-Qawasmi RA, Hartsfield JK, Everett ET, Flury L, Liu L, Foroud TM, et al. Genetic predisposition to external apical root resorption. Am J Orthod Dentofacial Orthop. 2003 Mar;123(3):242-52. (2003)	USA	n=118 (73 siblings and 45 parents) / Pretreatment and postreatment	12.1 (1.89)	Full-banded comprehensive treatment	Harris et al. (1997)	Lateral cephalometric Panoramic radiographs	Maxillary central incisor, Mandibular central incisor, Mandibular first molar, mesial root and Mandibular first molar, distal root	Class I Class II Class III
Al-Qawasmi et al.²⁷27 Al-Qawasmi RA, Hartsfield JK, Everett ET, Flury L, Liu L, Foroud TM, et al. Genetic predisposition to external apical root resorption in orthodontic patients: linkage of chromosome-18 marker. J Dent Res. 2003 May;82(5):356-60. (2003)	USA	n=124 (79 siblings and 45 parents)	12.3 (1.82)	Full-banded comprehensive treatment	Harris et al. (1997)	Lateral cephalometric Panoramic radiographs	Maxillary central incisor, Mandibular central incisor, Mandibular first molar, mesial root and Mandibular first molar, distal root	Class I Class II Class III
Bastos Lages et al.⁶6 Bastos Lages EM, Drummond AF, Pretti H, Costa FO, Lages EJP, Gontijo AI, et al. Association of functional gene polymorphism IL-1beta in patients with external apical root resorption. Am J Orthod Dentofacial Orthop. 2009 Oct;136(4):542-6. (2009)	Brazil	n = 61 EARR = 23 Control = 38	18.9 (5.2)	Straight wire	Linge and Linge’s method (1991) modified by Brezniak (2004)	Periapical radiographs	Maxillary incisors (central and lateral)	Class I Class II Class III
Sharab et al.²2 Sharab LY, Morford LA, 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 Apr;18(Suppl 1):71-82. (2015)	USA	n = 134 EARR = 67 Control = 67	EARR: 15.78 (1.13) Control: 15.79 (1.14)	Edgewise	Malmgren et al. (1982)	Panoramic radiographs Occlusal radiographs	Maxillary incisors (central and lateral)	NR
Gülden et al.²⁸28 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 Jan;70(1):20-38. (2009)	Germany	n = 258 EARR = 96 Control = 162	NR	NR	Linge and Linge’s method (1983)	Panoramic radiographs scanned	Canines, premolars and molars (mesial and distal roots)	NR
Iglesias-Linares et al.²⁹29 Iglesias-Linares A, Sonnenberg B, Solano B, Yañez-Vico RM, Solano E, Lindauer SJ, et al. Orthodontically induced external apical root resorption in patients treated with fixed appliances vs removable aligners. Angle Orthod. 2017 Jan;87(1):3-10. (2017)	Spain	n=372 EARR = 174 Control = 198	NR	Removable aligners Straight wire	Harris et al. (1997) Al-Qawasmi et al. (2003)	Panoramic radiographs	Maxillary incisors (central and lateral)	Class I Class II Class III
Iglesias-Linares et al.⁴⁷47 Iglesias-Linares A, Yañez-Vico RM, Ortiz-Ariza E, Ballesta S, Mendoza-Mendoza A, Perea E, et al. Postorthodontic external root resorption in root-filled teeth is influenced by interleukin-1ß polymorphism. J Endod. 2012 Mar;38(3):283-748. (2013)	Spain	n = 93 EARR = 39 Control = 54	EARR: 24.54 (5.85) Control: 23.89 (5.72)	Straight wire	According to Linge and Linge’s method (1991) modified by Brezniak (2004)	Lateral cephalometric Panoramic radiographs	Upper second root-filled premolars	Class I Class II Class III
Fontana et al.²⁰20 Fontana MLSSN, Souza CM, Bernardino JF, Hoette F, Hoette ML, Thum L, et al. Association analysis of clinical aspects and vitamin D receptor gene polymorphism with external apical root resorption in orthodontic patients. Am J Orthod Dentofacial Orthop. 2012 Sep;142(3):339-47. (2012)	Brazil	n = 377 EARR = 339 Control = 38	14.9 (NR)	Edgewise or Straight wire techniques	According to Linge and Linge’s method (1991)	Periapical radiographs	Maxillary central incisors	Class II, division 1
Iglesias-Linares et al.¹²12 Iglesias-Linares A, Yañez-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 Mar;18(2):198-205. (2012)	Spain	n = 73 EARR = 30 Control = 43	23.78 (5.91)	Straight Wire	Linge and Linge (1991) modified by Brezniak (2004)	Lateral cephalometric Panoramic radiographs	Upper premolars (vital and rooted teeth. Split-mouth and parallel group design)	Class I Class II Class III
Pereira et al.¹⁸18 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 Oct;20(7):659-67. (2014)	Portugal	n = 195 Pretreatment and postreatment	17.24 (6.8)	Hyrax and Straight wire	Linge and Linge’s method (1991) modified by Brezniak (2004)	Lateral cephalometric Panoramic radiographs	Maxillary incisors (central, lateral) Maxillary canines	Class I Class II Class III
Linhartova et al.⁷7 Linhartova P, Cernochova P, Izakovicova Holla L. IL1 gene polymorphisms in relation to external apical root resorption concurrent with orthodontia. Oral Dis. 2013 Apr;19(3):262-70. (2013)	Czech Republic	n = 106 EARR = 32 Control = 74	15.2 (5.0)	Straight wire or segmental technique	Linge and Linge’s method (1991) modified by Brezniak (2004)	Lateral cephalometric Panoramic radiographs	Maxillary incisors (central and lateral)	Class I Class II Class III
Guo et al.⁹9 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 Aug;150(2):283-9. (2016)	Han Chinese	n = 174 Pretreatment and postreatment	14.07 (3.1)	Straight wire	NR	Cone beam computed tomography	Maxillary incisors (left central)	Class I Class II Class III
Iglesias-Linares et al.²¹21 Iglesias-Linares A, Yañez-Vico RM, Moreno-Fernández AM, Mendoza-Mendoza A, Orce-Romero A, Solano-Reina E. Osteopontin gene SNPs (rs9138, rs11730582) mediate susceptibility to external root resorption in orthodontic patients. Oral Dis. 2014 Apr;20(3):307-12. (2014)	Spain	n = 87 EARR = 37 Control = 50	EARR: 24.7 (5.95) Control: 23.8 (5.33)	Straight wire	Linge and Linge’s method (1991) modified by Brezniak (2004)	Lateral cephalometric Panoramic radiographs	Maxillary incisors (central, lateral)	Class I Class II Class III
Tomoyasu et al.¹⁷17 Tomoyasu Y, Yamaguchi T, Tajima A, Inoue I, Maki K. External apical root resorption and the interleukin-1B gene polymorphism in the Japanese population. Orthod Waves. 2009 Dec;68(4):152-7. (2009)	Japan	n = 54 Case (EARR > 2.0 mm) = NR Control (EARR < 2.0 mm) = NR	NR	NR	Harris et al. (1997)	Lateral cephalometric Panoramic radiographs	Maxillary and mandibular central incisors Mandibular first molar mesial root and distal root	Class I Class II Class III
*Borilova Linhartova et al.¹⁹19 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 Jan;23(1):29-35. (2017)	Czech Republic	n = 99 EARR = 30 Control = 69	EARR: 14.6 (3.2) Control: 15.2 (5.3)	Fixed orthodontic appliance therapy	Linge and Linge’s method (1991) modified by Brezniak (2004)	Lateral cephalometric Panoramic radiographs	Maxillary incisors (central, lateral)	Class I Class II Class III

Authors/Year	Study Type	Conclusion
Pinheiro et al.³3 Pinheiro LHM, Guimarães LS, Antunes LS, Küchler EC, Kirschneck C, Antunes LAA. Genetic variation involved in the risk to external apical root resorption in orthodontic patients: a systematic review. Clin Oral Investig. 2021 Oct;25(10):5613-27. (2021)	Systematic review and meta-analyses	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. The 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 according to GRADE
*Nowrin et al.⁴4 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 Nov;48(6):395-404. (2018)	Systematic review and meta-analyses	More research on the relationship between gene polymorphism and EARR is necessary to determine better specificity of possible interactions.
Wu et al.²³23 Wu FL, Wang LY, Huang YQ, Guo WB, Liu CD, Li SG. Interleukin-1ß +3954 polymorphisms and risk of external apical root resorption in orthodontic treatment: a meta-analysis. Genet Mol Res. 2013 Oct;12(4):4678-86. (2013)	Meta-analyses	The variant genotypes (CC and CT) on polymorphism to IL-1B were not associated with EARR risk, compared with the wild-type TT homozygote
Aminoshariae et al.²⁴24 Aminoshariae A, Aminoshariae A, Valiathan M, Kulild JC. Association of genetic polymorphism and external apical root resorption. Angle Orthod. 2016 Nov;86(6):1042-9. (2016)	Systematic review	The current investigation suggests guidelines and recommendations for future investigators studying genetic polymorphism in patients undergoing orthodontic treatment
Nieto-Nieto et al.⁴⁵45 Nieto-Nieto N, Solano JE, Yañez-Vico R. External apical root resorption concurrent with orthodontic forces: the genetic influence. Acta Odontol Scand. 2017 May;75(4):280-7. (2017)	Literature review	In recent years, international research groups have determined the degree of influence of some genetic biomarkers in the definition of increased/reduced susceptibility to post-orthodontic EARR. The influences of the gene cluster IL1 (IL1B, IL1A, IL1RN, IL6), P2RX7, CASP1, OPG (TNFRSF11B), RANK (TNFRSF11A), Osteopontin (OPN), TNFa, the vitamin D receptor (TaqI), TNSALP and IRAK1 were the most analyzed
Pereira et al.⁴⁶46 Pereira SA, Melo A, Resende E, Regateiro F, Coimbra Silva H. Antagonistic effect of IL1 variants in periodontitis and external apical root resorption: Evidence from a literature review. Arch Oral Biol. 2018 Nov;95:195-201. (2018)	Literature review	This study was performed searching for the association of rs1800587 from Interleukin-1 alpha (IL1A) gene and rs1143634 from interleukin-1 beta (IL1B) gene with EARR. In conclusion, suggests that for IL1B SNP rs1143634 and EARR have an opposite genetic profile. For IL1A, the hypothesis could not be confirmed
Behnaz et al.⁵⁰50 Behnaz M, Jazaeri M, Aghandeh P, Taheri M, Ghafouri-Fard. Genetic factors in determination of risk of external apical root resorption: a concise review. Gene Rep. 2020;21:100850. (2020)	Concise review	The rs1800587 and rs1143634 in IL-1A and IL-1B genes have been the mostly assessed SNPs in different populations. Yet, the results of investigations in different populations are not consistent. In this study, the authors summarize the results of studies that assessed the contribution of genetic factors in EARR. As genetic factors are involved in conferring risk of EARR, evaluation of these variants prior to establishment of orthodontic treatments might help in identification of at-risk individuals and better follow-up of these patients

[1] liviaazeredo@gmail.com

Brasil

Brasil

Bibliometric analysis of publications on genetic polymorphism and external apical root resorption research

RESUMO

Objetivo:

Métodos:

Resultados:

Conclusão: