Association Signals Unveiled by a Comprehensive Gene Set Enrichment Analysis of Dental Caries Genome-Wide Association Studies

Gene set-based analysis of genome-wide association study (GWAS) data has recently emerged as a useful approach to examine the joint effects of multiple risk loci in complex human diseases or phenotypes. Dental caries is a common, chronic, and complex disease leading to a decrease in quality of life worldwide. In this study, we applied the approaches of gene set enrichment analysis to a major dental caries GWAS dataset, which consists of 537 cases and 605 controls. Using four complementary gene set analysis methods, we analyzed 1331 Gene Ontology (GO) terms collected from the Molecular Signatures Database (MSigDB). Setting false discovery rate (FDR) threshold as 0.05, we identified 13 significantly associated GO terms. Additionally, 17 terms were further included as marginally associated because they were top ranked by each method, although their FDR is higher than 0.05. In total, we identified 30 promising GO terms, including 'Sphingoid metabolic process,' 'Ubiquitin protein ligase activity,' 'Regulation of cytokine secretion,' and 'Ceramide metabolic process.' These GO terms encompass broad functions that potentially interact and contribute to the oral immune response related to caries development, which have not been reported in the standard single marker based analysis. Collectively, our gene set enrichment analysis provided complementary insights into the molecular mechanisms and polygenic interactions in dental caries, revealing promising association signals that could not be detected through single marker analysis of GWAS data. © 2013 Wang et al

Explaining gender differences in caries: a multifactorial approach to a multifactorial disease.

Many studies have demonstrated that caries rates are higher in women than in men. This review attempts to provide an explanation for this trend by examining each factor which contributes to caries and how the factor differs in men and women. Evidence has been provided to demonstrate that caries risk factors for women include a different salivary composition and flow rate, hormonal fluctuations, dietary habits, genetic variations, and particular social roles among their family. Systemic diseases that have been found to be associated with caries have also been found to have an association with the female gender. An extended exposure to the oral cavity or a more cariogenic oral microflora has not been proven to contribute to higher caries in women. Further research in these areas could be done in the future to explain their contribution, or lack thereof, to a higher caries rate in women

Role of estrogen related receptor beta (ESRRB) in DFN35B hearing impairment and dental decay

BACKGROUND: Congenital forms of hearing impairment can be caused by mutations in the estrogen related receptor beta (ESRRB) gene. Our initial linkage studies suggested the ESRRB locus is linked to high caries experience in humans. METHODS: We tested for association between the ESRRB locus and dental caries in 1,731 subjects, if ESRRB was expressed in whole saliva, if ESRRB was associated with the microhardness of the dental enamel, and if ESRRB was expressed during enamel development of mice. RESULTS: Two families with recessive ESRRB mutations and DFNB35 hearing impairment showed more extensive dental destruction by caries. Expression levels of ESRRB in whole saliva samples showed differences depending on sex and dental caries experience. CONCLUSIONS: The common etiology of dental caries and hearing impairment provides a venue to assist in the identification of individuals at risk to either condition and provides options for the development of new caries prevention strategies, if the associated ESRRB genetic variants are correlated with efficacy.Fil: Weber, Megan L.. University of Pittsburgh; Estados UnidosFil: Hsin, Hong Yuan. University of Pittsburgh; Estados UnidosFil: Kalay, Ersan. Karadeniz Technical University; TurquíaFil: Brožková, Dana Š. Charles University; República Checa. University Hospital Motol; República ChecaFil: Shimizu, Takehiko. Nihon University. School of Dentistry; JapónFil: Bayram, Merve. Medipol Istanbul University; TurquíaFil: Deeley, Kathleen. University of Pittsburgh; Estados UnidosFil: Küchler, Erika C.. University of Pittsburgh; Estados UnidosFil: Forella, Jessalyn. University of Pittsburgh; Estados UnidosFil: Ruff, Timothy D.. University of Pittsburgh; Estados UnidosFil: Trombetta, Vanessa M.. University of Pittsburgh; Estados UnidosFil: Sencak, Regina C.. University of Pittsburgh; Estados UnidosFil: Hummel, Michael. University of Pittsburgh; Estados UnidosFil: Briseño Ruiz, Jessica. University of Pittsburgh; Estados UnidosFil: Revu, Shankar K.. University of Pittsburgh; Estados UnidosFil: Granjeiro, José M.. Universidade Federal Fluminense; BrasilFil: Antunes, Leonardo S.. Universidade Federal Fluminense; BrasilFil: Antunes, Livia A.. Universidade Federal Fluminense; BrasilFil: Abreu, Fernanda V.. Universidade Federal Fluminense; BrasilFil: Costabel, Marcelo C.. Universidade Federal do Rio de Janeiro; BrasilFil: Tannure, Patricia N.. Veiga de Almeida University; Brasil. Salgado de Oliveira University; BrasilFil: Koruyucu, Mine. Istanbul University; TurquíaFil: Patir, Asli. Medipol Istanbul University; TurquíaFil: Poletta, Fernando Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mereb, Juan C.. Estudio Colaborativo Latino Americano de Malformaciones Congénitas; ArgentinaFil: Castilla, Eduardo Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. CEMIC-CONICET. Centro de Educaciones Médicas e Investigaciones Clínicas ; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Orioli, Iêda M.. Universidade Federal do Rio de Janeiro; BrasilFil: Marazita, Mary L.. University of Pittsburgh; Estados UnidosFil: Ouyang, Hongjiao. University of Pittsburgh; Estados UnidosFil: Jayaraman, Thottala. University of Pittsburgh; Estados UnidosFil: Seymen, Figen. Istanbul University; TurquíaFil: Vieira, Alexandre R.. University of Pittsburgh; Estados Unido

Outcomes in Trials for Management of Caries Lesions (OuTMaC):protocol

Background Clinical trials on caries lesion management use an abundance of outcomes, hampering comparison or combination of different study results and their efficient translation into clinical practice. Core outcome sets are an agreed standardized collection of outcomes which should be measured and reported in all trials for a specific clinical area. We aim to develop a core outcome set for trials investigating management of caries lesions in primary or permanent teeth conducted in primary or secondary care encompassing all stages of disease. Methods To identify existing outcomes, trials on prevention and trials on management of caries lesions will be screened systematically in four databases. Screening, extraction and deduplication will be performed by two researchers until consensus is reached. The definition of the core outcome set will by based on an e-Delhi consensus process involving key stakeholders namely patients, dentists, clinical researchers, health economists, statisticians, policy-makers and industry representatives. For the first stage of the Delphi process, a patient panel and a separate panel consisting of researchers, clinicians, teachers, industry affiliated researchers, policy-makers, and other interested parties will be held. An inclusive approach will be taken to involve panelists from a wide variety of socio-economic and geographic backgrounds. Results from the first round will be summarized and fed back to individuals for the second round, where panels will be combined and allowed to modify their scoring in light of the full panel’s opinion. Necessity for a third round will be dependent on the outcome of the first two. Agreement will be measured via defined consensus rules; up to a maximum of seven outcomes. If resources allow, we will investigate features that influence decision making for different groups. Discussion By using an explicit, transparent and inclusive multi-step consensus process, the planned core outcome set should be justifiable, relevant and comprehensive. The dissemination and application of this core outcome set should improve clinical trials on managing caries lesions and allow comparison, synthesis and implementation of scientific data. Trial registration Registered 12 April 2015 at COMET (http://www.comet-initiative.org

Effects of dental probing on occlusal surfaces - A scanning electron microscopy evaluation

The aim of this clinical-morphological study was to investigate the effects of dental probing on occlusal surfaces by scanning electron microscopy (SEM). Twenty sound occlusal surfaces of third molars and 20 teeth with initial carious lesions of 17- to 26-year-old patients (n = 18) were involved. Ten molars of each group were probed with a sharp dental probe (No. 23) before extraction; the other molars served as negative controls. After extraction of the teeth, the crowns were separated and prepared for the SEM study. Probing-related surface defects, enlargements and break-offs of occlusal pits and fissures were observed on all occlusal surfaces with initial carious lesions and on 2 sound surfaces, respectively. No traumatic defects whatsoever were visible on unprobed occlusal surfaces. This investigation confirms findings of light-microscopic studies that using a sharp dental probe for occlusal caries detection causes enamel defects. Therefore, dental probing should be considered as an inappropriate procedure and should be replaced by a meticulous visual inspection. Critical views of tactile caries detection methods with a sharp dental probe as a diagnostic tool seem to be inevitable in undergraduate and postgraduate dental education programmes. Copyright (c) 2007 S. Karger AG, Basel

Bayesian semiparametric inference for multivariate doubly-interval-censored data

Based on a data set obtained in a dental longitudinal study, conducted in Flanders (Belgium), the joint time to caries distribution of permanent first molars was modeled as a function of covariates. This involves an analysis of multivariate continuous doubly-interval-censored data since: (i) the emergence time of a tooth and the time it experiences caries were recorded yearly, and (ii) events on teeth of the same child are dependent. To model the joint distribution of the emergence times and the times to caries, we propose a dependent Bayesian semiparametric model. A major feature of the proposed approach is that survival curves can be estimated without imposing assumptions such as proportional hazards, additive hazards, proportional odds or accelerated failure time.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS368 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Silver Diamine Fluoride and Oral Health-Related Quality of Life

Purpose: The purpose of this study was to study the association between Silver Diamine Fluoride (SDF) and Oral Health-Related Quality of Life as assessed by “The Early Childhood Oral Health Impact Scale” questionnaire. Methods: Parents of healthy children (ASA I and II) ages 1-5 with early childhood caries with reversible pulpitis who had application of SDF filled out a questionnaire at baseline and again after one month. The questionnaire was designed to evaluate the child’s behavior, physical abilities, pain, temperament, and how well the child gets along with others. Results: Wilcoxon Signed Rank Test was used to determine if responses to various ECOHIS items and the total scores were different between the two time points. Conclusion: Children with dental caries who had application of SDF reported less dental pain, less eating problems, higher quality of sleep and overall higher quality of life at one-month follow up compared with the baseline

Does chewing xylitol gum improve oral health?

Popular chewing gum brands such as Orbit and Trident advertise that chewing their gum promotes oral health due to the presence of xylitol. This compound has interested oral health researchers since the 1970 s, but recent advances in research have been used to market it to the public as a prophylactic. Xylitol is a sugar that cannot be fermented by virtually any bacterial species, including Streptococcus mutans (S. mutans), the main contributor to dental caries (tooth cavities). The sugar alcohol negatively affects the pathogen in two different ways: it decreases plaque adhesiveness and inhibits growth. I have analyzed experiments from leading oral health researchers that aimed to determine how xylitol affects S. mutans, the optimal dose of xylitol for S. mutans inhibition, short-term and long-term benefits of xylitol, and limitations of xylitol being sold to different socioeconomic classes. While legitimate platforms for xylitol distribution still need to be expanded, the benefits of xylitol are literally worth salivating over. As governments look to improve health care practices for their citizens, xylitol products should be considered as a legitimate means of reducing oral health maladies.Honors CollegeThesis (B.?.

Explaining gender differences in caries: a multifactorial approach to a multifactorial disease.

Many studies have demonstrated that caries rates are higher in women than in men. This review attempts to provide an explanation for this trend by examining each factor which contributes to caries and how the factor differs in men and women. Evidence has been provided to demonstrate that caries risk factors for women include a different salivary composition and flow rate, hormonal fluctuations, dietary habits, genetic variations, and particular social roles among their family. Systemic diseases that have been found to be associated with caries have also been found to have an association with the female gender. An extended exposure to the oral cavity or a more cariogenic oral microflora has not been proven to contribute to higher caries in women. Further research in these areas could be done in the future to explain their contribution, or lack thereof, to a higher caries rate in women