| Autor: |
Iber-Díaz P; Section of Orthodontics, School of Dentistry, Complutense University, 28040 Madrid, Spain., Senen-Carramolino R; Section of Orthodontics, School of Dentistry, Complutense University, 28040 Madrid, Spain., Iglesias-Linares A; Section of Orthodontics, School of Dentistry, Complutense University, 28040 Madrid, Spain.; BIOCRAN Craniofacial Biology Research Group, Complutense University, 28040 Madrid, Spain., Fernández-Navarro P; Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, 28029 Madrid, Spain.; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain., Flores-Mir C; Professor and Interim Graduate Orthodontic Program Director, School of Dentistry, University of Alberta, Edmonton, AB T6G 1C9, Canada., Yañez-Vico RM; Section of Orthodontics, School of Dentistry, Complutense University, 28040 Madrid, Spain.; BIOCRAN Craniofacial Biology Research Group, Complutense University, 28040 Madrid, Spain. |
| Abstrakt: |
Personalized dental medicine requires from precise and customized genomic diagnostic. To conduct an association analysis over multiple putative loci and genes located at chromosomes 2, 4, 8, 12, 18, X, and Y, potentially implicated in an extreme type of external apical root resorption secondary to orthodontic forces (aEARR). A genome-wide association study of aEARR was conducted with 480 patients [ratio~1:3 case/control]. Genomic DNA was extracted and analyzed using the high-throughput Axiom platform with the GeneTitan ® MC Instrument. Up to 14,377 single nucleotide polymorphisms (SNPs) were selected at candidate regions and clinical/diagnostic data were recorded. A descriptive analysis of the data along with a backward conditional binary logistic regression was used to calculate odds ratios, with 95% confidence intervals [ p < 0.05]. To select the best SNP candidates, a logistic regression model was fitted assuming a log-additive genetic model using R software [ p < 0.0001]. In this sample the top lead genetic variants associated with aEARR were two novel putative genes located in the X chromosome, specifically, STAG 2 gene, rs151184635 and RP1-30E17.2 gene, rs55839915. These variants were found to be associated with an increased risk of aEARR, particularly restricted to men [OR: 6.09; 95%CI: 2.6-14.23 and OR: 6.86; 95%CI: 2.65-17.81, respectively]. Marginal associations were found at previously studied variants such as SSP1 : rs11730582 [OR: 0.54; 95%CI: 0.34-0.86; p = 0.008], P2RX7 : rs1718119 [OR: 0.6; 95%CI: 0.36-1.01; p = 0.047], and TNFRSF11A : rs8086340 [OR: 0.6; 95%CI: 0.38-0.95; p = 0.024]), found solely in females. Multiple putative genetic variants located at chromosomes X and Y are potentially implicated in an extreme phenotype of aEARR. A gender-linked association was noted. |
