title: Genetic and treatment-related risk factors associated with external apical root resorption (EARR) concurrent with orthodontia.
abstract: 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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Oral Health Practice, University of Kentucky College of Dentistry, Lexington, KY, USA.
authors: L Y
authors: LY
authors: Sharab
authors: Department of Oral Health Science, University of Kentucky College of Dentistry, Lexington, KY, USA.
authors: L A
authors: LA
authors: Morford
authors: Department of Oral Health Science, University of Kentucky College of Dentistry, Lexington, KY, USA.
authors: J
authors: J
authors: Dempsey
authors: Hereditary Genomics Laboratory, Center for Oral Health Research, University of Kentucky College of Dentistry, Lexington, KY, USA.
authors: G
authors: G
authors: Falcão-Alencar
authors: Department of Oral Health Science, University of Kentucky College of Dentistry, Lexington, KY, USA.
authors: A
authors: A
authors: Mason
authors: Hereditary Genomics Laboratory, Center for Oral Health Research, University of Kentucky College of Dentistry, Lexington, KY, USA.
authors: E
authors: E
authors: Jacobson
authors: Department of Oral Health Science, University of Kentucky College of Dentistry, Lexington, KY, USA.
authors: G T
authors: GT
authors: Kluemper
authors: Department of Orthodontics and Oral Facial Genetics, Indiana University School of Dentistry, Indianapolis, IN, USA.
authors: J V
authors: JV
authors: Macri
authors: Department of Oral Health Science, University of Kentucky College of Dentistry, Lexington, KY, USA.
authors: J K
authors: JK
authors: Hartsfield
mesh_terms: D000293:Adolescent; D000328:Adult; D001641:Bicuspid / Q000601:surgery; D016022:Case-Control Studies; D020170:Caspase 1 / Q000235:genetics; D002508:Cephalometry / Q000706:statistics & numerical data; D002648:Child; D004247:DNA / Q000235:genetics; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D053582:Interleukin-1alpha / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009971:Orthodontics, Corrective / Q000009:adverse effects*; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D058486:Receptors, Purinergic P2X7 / Q000235:genetics; D012307:Risk Factors; D012391:Root Resorption / Q000209:etiology / Q000235:genetics*; D013997:Time Factors; D019227:Tooth Apex / Q000473:pathology*; D014081:Tooth Extraction / Q000706:statistics & numerical data; D055815:Young Adult
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7; D004247:DNA; D020170:Caspase 1
keywords: caspase-1; external apical root resorption; interleukin-1; interleukin-1 receptor antagonist; purinergic-receptor-P2X ligand-gated ion channel 7