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. 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.
Subject(s)
Orthodontics, Corrective/adverse effects , Root Resorption/genetics , Tooth Apex/pathology , Adolescent , Adult , Bicuspid/surgery , Case-Control Studies , Caspase 1/genetics , Cephalometry/statistics & numerical data , Child , DNA/genetics , Female , Genetic Variation/genetics , Genotype , Humans , Interleukin 1 Receptor Antagonist Protein/genetics , Interleukin-1alpha/genetics , Interleukin-1beta/genetics , Male , Middle Aged , Polymorphism, Genetic/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Purinergic P2X7/genetics , Risk Factors , Root Resorption/etiology , Time Factors , Tooth Extraction/statistics & numerical data , Young AdultABSTRACT
The role played by genetic components in the etiology of the Class III phenotype, a class of dental malocclusion, is not yet understood. Regions that may be related to the development of Class III malocclusion have been suggested previously. The aim of this study was to search for genetic linkage with 6 microsatellite markers (D1S234, D4S3038, D6S1689, D7S503, D10S1483, and D19S566), near previously proposed candidate regions for Class III. We performed a two-point parametric linkage analysis for 42 affected individuals from 10 Brazilian families with a positive Class III malocclusion segregation. Analysis of our data indicated that there was no evidence for linkage of any of the 6 microsatellite markers to a Class III locus at = zero, with data supporting exclusion for 5 of the 6 markers evaluated. The present work reinforces that Class III is likely to demonstrate locus heterogeneity, and there is a dependency of the genetic background of the population in linkage studies.
