Title: Genetic Association Analysis of Novel Markers on Chromosome-17 With Dental-Agenesis
Katie Gibson (Presenter)
University of Kentucky College of Dentistry
James Hartsfield, University of Kentucky
Chi Wang, University of Kentucky, College of Public Health
Lorri Morford, University of Kentucky
Objectives: Dental-agenesis has been associated with other medical conditions, including colorectal and ovarian cancer. While the WNT/AXIN pathway may play a role in this type of dual phenotype, few studies have explored cancer-associated-markers for their novel association to dental-agenesis in healthy patients. This study examined single-nucleotide-polymorphisms (SNP) on chromosome-17 that were previously associated with cancer as potential markers of dental-agenesis. Our null hypothesis stated that there would be no association between the SNPs (rs7405776, rs7501939, rs9303542, rs2084881, rs183211, rs9730) and patients with dental-agenesis compared to controls.
Methods: Ethics oversight was obtained from the University-of-Kentucky-IRB. Following informed consent, saliva and family medical/dental history was obtained from biologically-unrelated Caucasian subjects diagnosed with hypodontia (agenesis of 1-to-5 non-3rd-molar-teeth in the adult-dentition), oligodontia (agenesis of ≧6 adult non-3rd-molar-teeth) or no-agenesis (controls). Genomic-DNA isolated from the saliva was used for genotyping, and results were compared between groups.
Results: To date, 121 Caucasian subjects have been recruited consisting of 41-hypodontia-cases, 7-oligodontia-cases, and 73-controls. The predominant teeth affected by agenesis in this population were the mandibular-2nd-premolars, maxillary-lateral-incisors, and maxillary-2nd-premolars. Our preliminary data show a potential genotypic shift for both SNPs rs183211 (GG/AG/AA) and rs9730 (CC/CG/GG) when comparing hypodontia-cases and controls; where rs183211 yielded (71.1%/26.3%/2.6%) versus (58.5%/33.8%/7.7%), and rs9730 showed (74.3%/25.7%/0%) versus (76.1%/17.4%/6.5%), respectively. Recruitment is ongoing, and final statistical observations will be summarized in the presentation.
Conclusions: Both rs183211 and rs9730 reside on 17q21.32 within the N-Ethylmaleimide-Sensitive-Factor (NSF) and Pleckstri-Homology-Domain-Containing-Family-M-Member-1 (PLEKHM1) genes, respectively. While any potential role of these SNPs (and genes) remains to be determined in connection with dental agenesis, based on literature findings we know that NSF protein functions as a vesicle fusing ATPase, while PLEKHM1 plays a key role in bone resorption and may participate in osteoclast intracellular vesicle transport.