Dental caries is the most prevalent chronic disease seen in children worldwide, and despite advancements in oral healthcare, many adults and children are still affected. The etiology of dental caries is complex, including environmental and genetic factors. Environmental factors such as fluoride exposure, oral hygiene, salivary function, diet, and bacterial flora have all been studied and found to contribute to dental caries experience. However, little is known about the genetic causes of dental caries. Candidate genes involved in enamel formation, tooth development, and taste have all been studied and found to be associated with dental caries.
Matrix metalloproteinases are a multi-gene family responsible for degrading extracellular matrix (ECM) molecules. Their role in the oral environment involves ECM remodeling and degradation processes. Because the dentin of a tooth is composed primarily of an organic matrix, mostly collagen, it can pose as a potential substrate for MMP10. Recent initial GWAS results showed an association between MMP10 and dental caries [Personal Communication, Center for Craniofacial and Dental Genetics]. Based upon these initial GWAS findings, we performed a replication study to determine if the associations between MMP10 and dental caries seen in the initial GWAS were present in our population. We also studied genotype precision between our study and that of the initial GWAS. We genotyped 274 Caucasian individuals at SNP rs2276108 and 338 Caucasian individuals at SNP rs17293642 using a Taqman® SNP genotyping assay. Linear regression analysis using PLINK, adjusting for age, sex and site, found no association between the SNPs and dental caries in our sample population. Failure to replicate the initial GWAS findings in MMP10 suggests priority efforts should be given to exploring other candidate associations. The public health importance of identifying these genetic factors and understanding how they impact dental caries and other oral heatlh issues should open up new strategies for treatment and prevention and may elucidate new biological processes.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-04042011-205707 |
| Date | 29 June 2011 |
| Creators | Commander, Sara B |
| Contributors | David Finegold, M.D., Ph.D., Steven Wendell, Ph.D., Robin Grubs, Ph.D. |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-04042011-205707/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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