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Genome-wide Association Studies of Pit and Fissure Surface Caries and Smooth Surface Caries in the Permanent Dentition

Zeng, Zhen (2014) Genome-wide Association Studies of Pit and Fissure Surface Caries and Smooth Surface Caries in the Permanent Dentition. Master's Thesis, University of Pittsburgh. (Unpublished)

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Abstract

Dental caries (i.e., tooth decay) is one of the most prevalent public health problems. According to the 1999-2004 National Health and Nutrition Examination Survey, 92% adults 20 to 64 in the United States have had dental caries in their permanent teeth. The important role of genetics in the multi-factorial etiology of dental caries is well-established. However, few specific caries genes have been discovered and validated. Recent family-based analyses have suggested differential genetic factors for primary dentition caries and permanent dentition caries, as well as for pit and fissure surface caries and smooth surface caries. Therefore, to identify genetic variants implicated in dental caries, we performed separate genome-wide association studies for caries indices of the two types of surfaces in the permanent dentition in 1,017 self-reported whites (ages 14 to 56 years), adjusted for the effects of age, sex, presence of Streptococcus mutans, and home water fluoride level. Caries indices were derived based on visual assessment of each surface of each tooth. More than 1.2 million SNPs were either successfully genotyped or imputed and were tested for association. Two homologous genes located on separate arms of the X chromosomes were suggestively associated with dental caries: BCOR (Xp11.4) was implicated for pit and fissure surfaces (P-value = 3.9E-7), and BCORL1 (Xq26.1) was implicated for smooth surfaces (P-value = 5.5E-6). Mutations in BCOR cause oculofaciocardiodental syndrome, a Mendelian disease involving multiple dental anomalies, along with other facial and developmental defects. Associations of other genes with plausible biological functions in cariogenesis were also observed for pit and fissure surfaces (e.g., INHBA, P-value = 5.1E-6) and for smooth surfaces (e.g., CXCR1 and CXCR2, P-value = 1.5E-6). In summary, this study lends additional support for the notion that genes differentially affect cariogenesis across the surfaces of the permanent dentition, and nominates several novel caries genes for further investigation. Understanding the role of genes in dental caries may ultimately lead to improved detection of high-risk individuals for better and earlier preventative interventions and treatments.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Zeng, Zhenzhz43@pitt.eduZHZ43
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Thesis AdvisorFeingold, Eleanorfeingold@pitt.eduFEINGOLD
Committee MemberWang, Xiaojingxiaojing.wang@hgen.pitt.edu
Committee MemberShaffer, John Rjrs51@pitt.edu, john.r.shaffer@gmail.comJRS51
Date: 29 January 2014
Date Type: Publication
Defense Date: 1 October 2012
Approval Date: 29 January 2014
Submission Date: 3 December 2013
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 50
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Human Genetics
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: GWAS, dental caries, genetic epidemiology
Date Deposited: 29 Jan 2014 17:23
Last Modified: 15 Nov 2016 14:16
URI: http://d-scholarship.pitt.edu/id/eprint/20169

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