Association of Human Dental Agenesis and Polymorphisms on Chromosome 8q24

Objectives: Our laboratory has been interested in identifying novel dental development gene mutations that may play a role in other phenotypes within the body later in life. Based on published findings from multiple Ovarian Cancer (OvCA) genome-wide studies, we have examined 12 OvCA-susceptibility markers for associations to non-third-molar dental-agenesis in healthy orthodontic patients. Our goal was to extend the lab's previous findings of single-nucleotide-polymorphisms (SNPs) on chromosome 8q24 and hypodontia with an enlarged cohort. In addition, we have begun to sequence the exons of long-non-coding-RNA, LINC00824, which are in linkage-disequilibrium (LD) with both SNPs, to identify potential causal mutations for dental-agenesis.
Methods: Following informed consent, saliva was collected as a DNA source from 41-subjects diagnosed with hypodontia (agenesis of <5 teeth), 7-subjects diagnosed with oligodontia (agenesis of >6 teeth) and 69-control individuals with a complete dentition (excluding 3rd molars). Taqman® genotyping of rs10088218 and rs10098821 was done on all subjects, and statistical analysis completed with JMP-software. Sanger Sequencing of the LINC00824 exons in linkage disequilibrium with the markers, and comparison of the case/control sequences using GENEIOUS-software is underway.
Results: The most common agenic teeth were mandibular-2nd-premolars (n=27), followed by maxillary-lateral-incisors (n=22) and maxillary-2nd-premolars (n=15). The occurrence of the rs10098821 CC-genotype was associated with dental-agenesis in a 2-phenotype (2PHE) and 3-phenotype (3PHE) Fit Model (p=0.0009, control/hypodontia; p=0.003, control/hypodontia/oligodontia, respectively). SNP rs10098821-CC was associated with an increased number of agenic teeth in both models (2PHE, p=0.004; 3PHE, p=0.003) as-well-as rs10088218-GA in the 3PHE model (p=0.008), with 0.8 power or greater.
Conclusions: Significant associations of dental-agenesis have been localized to 8q24 at SNP markers rs10088218 and rs10098821. Because these markers are in LD with LINC00824, Sanger sequencing is being employed to identify casual mutations of hypodontia. Identified variations will be further studied for a duel association to dental agenesis and cancer.