Genetic and treatment-related risk factors associated with external apical root resorption (EARR) concurrent with orthodontia

L. Y. Sharab, L. A. Morford, J. Dempsey, G. Falcão-Alencar, A. Mason, E. Jacobson, G. T. Kluemper, J. V. Macri, J. K. Hartsfield

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Objective: As genetic variation accounts for two-thirds of the variation in external apical root resorption (EARR) concurrent with orthodontic treatment, we analyzed the association of selected genetic and treatment-related factors with EARR concurrent with orthodontic treatment. Setting and sample population: This case-control study of 134 unrelated, orthodontically treated Caucasian individuals was conducted in part at an Indiana Private Practice, Indiana University and the University of Kentucky. Methods: Utilizing a research data bank containing information from ~1450 orthodontically treated patients, pre- and post-treatment radiographs from 460 individuals were evaluated for EARR of the four permanent maxillary incisors. Sixty-seven unrelated Caucasians with moderate to severe EARR were identified and were age-/sex-matched with orthodontically treated Caucasian controls yielding 38 females and 29 males per group. Factors tested for an association with EARR included the following: 1) treatment duration, 2) extraction of maxillary premolars, 3) numerous cephalometric measurements, and 4) DNA polymorphisms within/near candidate genes in a pathway previously implicated in EARR such as the purinergic-receptor-P2X, ligand-gated ion channel 7 (P2RX7; rs208294, rs1718119, and rs2230912), caspase-1 (CASP1; rs530537, rs580253, and rs554344), interleukin-1 beta (IL1B; rs1143634), interleukin-1 alpha (IL1A; rs1800587), and interleukin-1 receptor antagonist (IL1RA; rs419598) genes. Stepwise logistic regression was utilized to identify the factors significantly associated (significance taken at or less than the layered Bonferroni correction alpha) with the occurrence of EARR. Results: A long length of treatment and the presence of specific genotypes for P2RX7 SNP rs208294 were significantly associated with EARR. Conclusion: EARR occurrence was associated with both genetic and treatment-related variables, which together explained 25% of the total variation associated with EARR in the sample tested.

Original languageEnglish
Pages (from-to)71-82
Number of pages12
JournalOrthodontics and Craniofacial Research
Issue numberS1
StatePublished - Apr 1 2015

Bibliographical note

Publisher Copyright:
© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


  • Caspase-1
  • External apical root resorption
  • Interleukin-1
  • Interleukin-1 receptor antagonist
  • Purinergic-receptor-P2X ligand-gated ion channel 7

ASJC Scopus subject areas

  • Orthodontics
  • Surgery
  • Oral Surgery
  • Otorhinolaryngology


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