IADR Abstract Archives
Association Analysis of Genetic Variation in WWTR1 and External-Apical-Root-Resorption
Objectives: This study examined four single nucleotide polymorphisms (SNPs) in the WW Domain Containing Transcription Regulator 1 (WWTR1) gene for potential association with External Apical Root Resorption (EARR) in patients completing orthodontia.
Methods: With IRB oversight from Indiana University and University of Kentucky, Caucasian patients receiving orthodontic treatment were recruited to study the genetic and treatment factors associated with EARR. Initial and final radiographs taken on over 460 Phase-II Orthodontic patients were assessed for maxillary incisor EARR by 3-independent examiners and 76 cases with moderate to severe EARR were identified. Each case was age and sex-matched with two controls (n=152; having little to no EARR). Data were collected on the patients concerning their length of time in treatment and whether maxillary premolars were extracted for orthodontia. Buccal cells from the inner cheek of the mouth were collected as a source of DNA for genetic testing. Taqman-based genotyping was conducted on the Roche LightCycler480 to determine the genotypes of the WWTR1-associated SNPs in four different Linkage Disequilibrium (LD) blocks spanning parts of the gene: rs6807742 (A/T; promoter variant), rs1344816 (G/T), rs2278476 (C/T), and rs9828792 (A/G).
Results: Of the 228 total patients identified to study, ~123 to 152 subjects have been completely genotyped for all four WWTR1 SNPs to date. Based on control genotyping data thus far, the four SNPs maintained Hardy-Weinberg Equilibrium (HWE). A preliminary analysis showed no associations between the individual SNP markers and EARR by Chi square. The remaining genotyping will be completed for the meeting presentation and potential associations will be examined on a per SNP basis with the Fisher’s Exact Test. A stepwise logistic regression (SLR) will be utilized to identify any genetic and/or treatment related factors associated with the occurrence of EARR. In a second SLR, we will include additional SNP data that our group has previously shown to be associated with EARR (e.g., P2RX7 and IL1b data). The Benjamini-Hochberg correction will be used to adjust for multiple testing.
Conclusions: The final results of this study should provide new insights as to whether variations in WWTR-1 play a role in the occurrence of EARR concurrent with orthodontia.
Methods: With IRB oversight from Indiana University and University of Kentucky, Caucasian patients receiving orthodontic treatment were recruited to study the genetic and treatment factors associated with EARR. Initial and final radiographs taken on over 460 Phase-II Orthodontic patients were assessed for maxillary incisor EARR by 3-independent examiners and 76 cases with moderate to severe EARR were identified. Each case was age and sex-matched with two controls (n=152; having little to no EARR). Data were collected on the patients concerning their length of time in treatment and whether maxillary premolars were extracted for orthodontia. Buccal cells from the inner cheek of the mouth were collected as a source of DNA for genetic testing. Taqman-based genotyping was conducted on the Roche LightCycler480 to determine the genotypes of the WWTR1-associated SNPs in four different Linkage Disequilibrium (LD) blocks spanning parts of the gene: rs6807742 (A/T; promoter variant), rs1344816 (G/T), rs2278476 (C/T), and rs9828792 (A/G).
Results: Of the 228 total patients identified to study, ~123 to 152 subjects have been completely genotyped for all four WWTR1 SNPs to date. Based on control genotyping data thus far, the four SNPs maintained Hardy-Weinberg Equilibrium (HWE). A preliminary analysis showed no associations between the individual SNP markers and EARR by Chi square. The remaining genotyping will be completed for the meeting presentation and potential associations will be examined on a per SNP basis with the Fisher’s Exact Test. A stepwise logistic regression (SLR) will be utilized to identify any genetic and/or treatment related factors associated with the occurrence of EARR. In a second SLR, we will include additional SNP data that our group has previously shown to be associated with EARR (e.g., P2RX7 and IL1b data). The Benjamini-Hochberg correction will be used to adjust for multiple testing.
Conclusions: The final results of this study should provide new insights as to whether variations in WWTR-1 play a role in the occurrence of EARR concurrent with orthodontia.