Talon Cusp Associates With MMP2 in a Cohort of Individuals Born With Oral Clefts.

OBJECTIVE: The aim of this study was to use dental development as a tool to subphenotype oral clefts and investigate the association of MMP2 with dentin-pulp complex anomalies, in order to identify dental anomalies that are a part of a "cleft syndrome." DESIGN: Two hundred and ninety individuals born with cleft lip and palate were evaluated and several clinical features, such as cleft completeness or incompleteness, laterality, and presence of dental anomalies were used to assess each individual's cleft status. We tested for overrepresentation of MMP2 single nucleotide polymorphism rs9923304 alleles depending on individuals having certain dental anomalies. Chi-square and Fisher exact tests were used in all comparisons (α = .05). RESULTS: All individuals studied had at least one dental anomaly outside the cleft area. Significant differences between individuals born with clefts with and without talon cusp (P = .04) were observed for the frequency of the MMP2 less common allele. CONCLUSION: All individuals born with cleft lip and palate had alterations of the dentition, and a quarter to half of the individuals had alterations of the internal anatomy of their teeth, which further indicates that dental anomalies can be considered as an extended phenotype for clefts. MMP2 was associated with talon cusp in individuals born with oral clefts.

IRE1 Less Common Homozygous Genotype in Families With Positive History of Cancer and Individuals Born With Cleft Lip/Palate.

ABSTRACT: The aim of this study was to test if the marker rs196929 in IRE1 associated with cleft lip and palate depending on the family history for cancer. A consecutive sample of 836 individuals were recruited between April and October of 2019 (303 born with cleft lip and palate, 256 relatives mostly of the maternal side of individuals born with cleft lip and palate, and 277 unaffected unrelated individuals). Parents or guardians of the children answered a questionnaire with basic demographic information about their children and their family history of cleft lip and palate and cancer. DNA was obtained from whole saliva and IRE1 rs196929 was genotyped using TaqMan chemistry and end-point analysis. Over-representation of alleles was determined using chi-square as implemented in PLINK using an alpha of 0.05. There was an excess of less common homozygotes of IRE1 rs196929 among relatives of individuals born with cleft lip and palate when they had positive family history of cancer in comparison with individuals born with cleft lip and palate or with unrelated unaffected individuals (P = 0.0006 and P < 0.001, respectively). This pattern was similar when families reported one type of cancer or multiple ones, or when cancer affecting females (breast or reproductive tract) or the structures of the gastro-intestinal tract were considered. These results provide support for a role of the ER stress IRE1-XPB1 pathway in the higher frequency of cancer in families of individuals born with cleft lip and palate.

Phenome-Wide Scan Finds Potential Orofacial Risk Markers for Cancer.

Cancer is a disease caused by a process that drives the transformation of normal cells into malignant cells. The late diagnosis of cancer has a negative impact on the health care system due to high treatment cost and decreased chances of favorable prognosis. Here, we aimed to identify orofacial conditions that can serve as potential risk markers for cancers by performing a phenome-wide scan (PheWAS). From a pool of 6,100 individuals, both genetic and epidemiological data of 1,671 individuals were selected: 350 because they were previously diagnosed with cancer and 1,321 to match to those individuals that had cancer, based on age, sex, and ethnicity serving as a comparison group. Results of this study showed that when analyzing the individuals affected by cancer separately, tooth loss/edentulism is associated with SNPs in AXIN2 (rs11867417 p = 0.02 and rs2240308 p = 0.02), and leukoplakia of oral mucosa is associated with both AXIN2 (rs2240308 p = 0.03) and RHEB (rs2374261 p = 0.03). These phenotypes did not show the same trends in patients that were not diagnosed with cancer, allowing for the conclusion that these phenotypes are unique to cases with higher cancer risk.

Differences in Proteomic Profiles Between Caries Free and Caries Affected Children

Abstract Objective: To determine if there are differences in protein profiles in saliva depending if children of caries-free versus caries affected. Material and Methods: A cohort of 91 children with ages between 6 and 19 years, along clinical status of caries experience. Protein profiles in saliva were determined using electrophoresis and the calculation of the percentage of a specific band at a specific molecular weight in relationship to the total protein in that sample (% of total) using molecular weight standards. This quantification was repeated for each protein band across a range of molecular weights for each sample. Chi-square, Fisher's exact, and Student t-tests were used to compare the distributions between caries-free and caries affected children (α=0.05). Results: Histatin was more likely to be non-detectable or reduced in caries-free children (OR=7.56; 95% CI 1.62-35.13) and these children had on average one less gel band detected by the assay we used. Conclusion: We have found differences in proteins between caries affected and caries-free children, suggesting that this line of investigation holds the promise of providing new tools for caries management.

The concept of exposure when selecting comparison groups for determining individual susceptibility to addiction to cigarette smoking.

Smoking is a leading cause of preventable death. The effect of tobacco is even more contundent in people with mental illness and, in general, cigarette smoking addiction is influenced by genetic factors. The opioid system is involved in the mesolimbic reward system, which is of great importance in addictive behaviors, such as smoking and is influenced by genes such as the OPRM1. The aim of this study was to evaluate if selecting a comparison group that include light smokers versus people that never smoked impacts the results of genetic association studies. In addition, to evaluate the genetic association in different groups of smokers by analyzing independent covariates such as mental illness and clinical dental data. All subjects were participants of the Dental Registry and DNA Repository project. Genotyping was carried out using TaqMan chemistry for two markers in OPRM1 (rs553202 and rs7755635). Logistic regression analyses were performed as implemented in PLINK. The established value for alpha was 5%, and the Hardy-Weinberg equilibrium was evaluated by the chi-square test with one degree of freedom for each marker. 1,897 patients were included, which were allocated to eight distinct groups, according to the frequency and quantity of cigarettes smoked and mental illness status. There was no significant association between the two markers in OPRM1 and smoking. When mental illness and dental clinical data (tooth loss, dental caries, and periodontitis) were used as covariates, there were associations between heavy smoking and OPRM1, when non-smokers were used as comparison. We did not have diet or microbiome data to consider for these dental analyses and suggest that these kinds of data should be always incorporated in the future. Significant results were found only when the covariables mental illness and oral clinical data were added to the analysis.

Complex patterns of response to oral hygiene instructions: longitudinal evaluation of periodontal patients.

BACKGROUND: Oral hygiene instruction is an intervention widely practiced but increased knowledge about oral health does not necessarily dramatically impact oral disease prevalence in populations. We aimed to measure plaque and bleeding in periodontal patients over time to determine patterns of patient response to oral hygiene instructions. METHODS: Longitudinal plaque and bleeding index data were evaluated in 227 periodontal patients to determine the impact of oral hygiene instructions. Over multiple visits, we determined relative plaque accumulation and gingival bleeding for each patient. Subsequently, we grouped them in three types of oral hygiene status in response to initial instructions, using the longitudinal data over the period they were treated and followed for their periodontal needs. These patterns of oral hygiene based on the plaque and gingival bleeding indexes were evaluated based on age, sex, ethnic background, interleukin 1 alpha and beta genotypes, diabetes status, smoking habits, and other concomitant diseases. Chi-square and Fisher's exact tests were used to determine if any differences between these variables were statistically significant with alpha set at 0.05. RESULTS: Three patterns in response to oral hygiene instructions emerged. Plaque and gingival bleeding indexes improved, worsened, or fluctuated over time in the periodontal patients studied. Out of all the confounders considered, only ethnic background showed statistically significant differences. White individuals more often than other ethnic groups fluctuated in regards to oral hygiene quality after instructions. CONCLUSIONS: There are different responses to professional oral hygiene instructions. These responses may be related to ethnicity.

Rethinking isolated cleft lip and palate as a syndrome.

OBJECTIVE: The goal of the present work was to use dental conditions that have been independently associated with cleft lip and palate (CL/P) as a tool to identify a broader collection of individuals to be used for gene identification that lead to clefts. STUDY DESIGN: We studied 1573 DNA samples combining individuals that were born with CL/P or had tooth agenesis, supernumerary teeth, molar incisor hypomineralization, or dental caries with the goal to identify genetic associations. We tested 2 single-nucleotide polymorphisms that were located in the vicinity of regions suggested to contribute to supernumerary teeth. Overrepresentation of alleles were determined for combinations of individuals as well as for each individual phenotypic group with an α of .05. RESULTS: We determined that the allele C of rs622260 was overrepresented in all individuals studied compared with a group of unrelated individuals who did not present any of the conditions described earlier. When subgroups were tested, associations were found for individuals with hypomineralization. CONCLUSIONS: Although we did not test this hypothesis directly in the present study, based on associations reported previously, we believe that CL/P is actually a syndrome of alterations of the dentition, and considering it that way may allow for the identification of genotype-phenotype correlations that may be useful for clinical care.

Medical sequencing of de novo ectodermal dysplasia in identical twins and evaluation of the potential eligibility for recombinant EDA therapy.

The purpose of this study was to test two 8-year-old identical twins with ectodermal dysplasia (ED) and their unaffected parents for the presence of mutations in the EDA gene with the hypothesis that they might be carrying a de novo mutation in EDA and potentially eligible for recombinant EDA therapy. DNA was extracted using saliva samples obtained from the identical twin girls and both parents. PCR products of Ectodyplasin A (EDA), Ectodysplasin Receptor (EDAR), Ectodysplasin Receptor Associated Death Domain (EDARADD), and Connexin-30 (GJB6) were sequenced by the Sanger method and the results analyzed using a reference sequence. Exons and exon-intron boundaries of EDA, EDAR, EDARADD, and GJB6 were sequenced in both parents and the affected identical twin pair. No mutations were detected in EDA or GJB6. Genetic variants located in the intron of EDAR were found but determined to be non-contributory to the twins' ED. A microsatellite polymorphism was detected in all four subjects in exon 4 of the EDARADD gene but determined not to be causal to the ED. There was a silent mutation detected in exon 6 of the EDARADD gene of both the daughters and their unaffected mother but also unlikely to be the cause of ED. These results suggest that ED of the subjects is caused by a de novo mutation in a gene not studied here. It is likely these subjects and their future offspring would not benefit from the development of recombinant EDA replacement therapy.

A Pragmatic Study Shows Failure of Dental Composite Fillings Is Genetically Determined: A Contribution to the Discussion on Dental Amalgams.

Composite resins for posterior tooth restorations have become a viable alternative to dental amalgam. Failures sometimes cannot be easily explained, and we hypothesize that a genetic component may influence longevity of restorations. We aimed to determine if there is any evidence for a difference in the performance of amalgams versus composite resin in extensive posterior restorations. We also aimed to determine if risk factors such as age, sex, smoking tobacco, alcohol drinking, diabetes status, and periodontal health status may have a role in the failures of extensive anterior composite restorations. Finally, we investigated if genetic variation in matrix metalloproteinases that are present in the mineralized dentin is associated with failure of composite resin. The data used to perform this research were obtained from the Dental Registry and DNA Repository project after screening 4,856 patients. All restorations were evaluated at times of 1, 2, and 5 years after the restoration placement. 6,266 amalgam and 2,010 composite restorations were analyzed in a total of 807 patients in a period of approximately 10 years (period corresponding to the database existence). An additional 443 extensive direct composite resin restorations in anterior teeth were also studied. Failure rates of amalgam and composite restorations are similar, and by the end of 5 years, composites outperformed amalgams slightly. Failures of anterior composite restorations occurred more often in males who smoked tobacco (p = 0.05), despite a similar number of females and males that smoked tobacco in the sample (116 individuals smoked tobacco, 54 females and 62 males). Alcohol drinking increased failure rate within 2 years (p = 0.03). We found a statistically significant association between matrix metalloproteinase 2 rs9923304 and failure of composite restorations (p = 0.007). Composite resins can replace amalgam restorations. Smoking tobacco and drinking alcohol will increase the chance of restoration failure.

Correlação dos hábitos de dieta e higiene oral de crianças com os níveis de Streptococcus mutans / Correlation between dietary and oral hygiene habits and the Streptococcus mutans levels in schoolchildren

Objetivo: Avaliar a correlação dos hábitos de dieta e higiene oral com os níveis de Streptococcus mutans (SM) e de biofilme entre escolares. Método: Oitenta e duas crianças de 6-8 anos de idade foram selecionadas para o estudo. Um questionário foi utilizado com os responsáveis pelas crianças. Utilizou-se o método da espátula de madeira para coleta de saliva, sendo pressionada sobre a placa Rodac®, contendo 12 ml do meio MSKB. As placas foram incubadas por 72 horas em jarra de anaerobiose, com atmosfera de N2 (80%), H2 (10%) e CO2 (10%) a 37°C. As UFC foram contadas, utilizando microscópio estereoscópio e expressas em escores, de acordo com o seguinte critério: *0 = Ausência de SM; *1 = Baixo (1-10UFC); *2 = Médio (11-100 UFC); *3 = Elevado (101-250 UFC); *4 =Muito Elevado (> 250 UFC). Para análise estatística usou-se o programa SPSS. Resultados: 82% das crianças tinham nível médio de SM. Níveis alto e muito alto de SM foram observados em 55% das crianças que consumiam doces entre as refeições (x2= 0,509). Apesar de não ter sido significante a relação entre nível de SM e hábitos de higiene oral (P = 0,228), observou-se que as crianças que escovavam seus dentes três vezes ou mais possuíam níveis baixos ou médios de SM. Conclusão: Os hábitos de dieta e higiene oral não mostraram correlação estatisticamente significante com níveis de SM, e essa correlação não foi encontrada com o índice de biofilme.

Transforming growth factor-alfa gene (TGFA), human tooth agenesis, and evidence of segmental uniparental isodisomy.

We have previously reported an association between variants in the transforming growth factor-alfa gene (TGFA) and human tooth agenesis. To demonstrate in greater detail that TGFA contributes to tooth agenesis, we investigated additional markers in the gene. Cheek swab samples were obtained for DNA analysis from 116 patient/parent trios. Probands had at least one developmentally missing tooth, excluding third molars. Genotyping was performed using TaqMan assays. Linkage disequilibrium analysis and test of the transmission distortion of the marker alleles were performed. We confirmed that TGFA variants and haplotypes are associated with tooth agenesis. Moreover, it appears that preferential premolar agenesis is associated with TGFA, and patients with a family history of tooth agenesis would have an associated haplotype. Finally, we excluded that a TGFA microdeletion could cause sporadic agenesis in a case of upper lateral incisors and lower second premolars and suggest this case may be consequence of a segmental uniparental isodisomy.

Studies of dental anomalies in a large group of school children.

The identification of specific patterns of dental anomalies would allow testing the hypothesis that certain genetic and environmental factors contribute to distinct dental anomaly subphenotypes. A sexual dimorphism in tooth agenesis and its association with other dental anomalies has been suggested. The aim of this study was to investigate a large group of children to define dental anomaly subphenotypes that may aid future genetic studies. Orthopantamograms of 1198 subjects were examined and 1167 were used in this study. The frequency of tooth agenesis in the studied population was 4.8%. Male:female ratios varied from 2:1 in the agenesis of upper lateral incisors to 0.5:1 in premolar agenesis. The risk of infra-occlusion of primary molars and double formation of primary incisors was increased in individuals with tooth agenesis.

Assessing the proposed association between tooth agenesis and taurodontism in 975 paediatric subjects.

BACKGROUND: An association between tooth agenesis and taurodontism has been suggested. The identification of subpopulations with specific associated dental anomalies (subphenotype) would allow testing of the specific hypothesis that certain genetic factors contribute to the specific subphenotype. AIM: This work aims to assess a large cohort to verify if the association between tooth agenesis and taurodontism is present. DESIGN: Panoramic radiographs of 1002 patients were examined and 975 were used in this study. The presence of tooth agenesis and taurodontism was assessed in the study population. RESULTS: The frequency of tooth agenesis was 4.6% and the frequency of taurodontism was 1.6%. There were, however, no observations of concomitant tooth agenesis and taurodontism. CONCLUSIONS: Our data do not support the hypothesis that isolated tooth agenesis is associated with isolated taurodontism.

Frequência da cárie de estabelecimento precoce e relação com a dieta a higiene bucal / Early childhood caries frequency and its relationship with diet and oral hygiene

O objetivo do estudo foi verificar o perfil de dieta e higiene bucal de bebês, a frequência e o padrão de acometimento da cárie de estabelecimento precoce (CEP), relacionando-os com o perfil identificado. Foram analisados 735 prontuários de uma clínica de bebês. Foi observado um elevado consumo de dieta noturna (73,7%), de açúcar (76%), e um grande número de pacientes recebendo higiene bucal (76,9%), bem como elevada frequência de CEP (29,8%). A relação entre CEP e dieta noturna, consumo de açúcar e higiene bucal foi estatisticamente significante. O padrão de acometimento da cárie foi diferente do encontrado na literatura. Nesta população, foi verificada uma relação positiva entre o consumo de dieta noturna e a frequência da CEP

Mamadeira: conteúdo, presença de sacarose e caracteríticas dos bicos / Bottles: content, presence of sucrose and characteristics of the nipples

O objetivo deste artigo foi correlacionar o tamanho dos orifícios dos bicos e a consistência do conteúdo das mamadeiras, assim como a utilização da sacarose e os tipos de alimentos usados. Cento e vinte três fichas da Clínica de Bebês de uma Instituição Pública de Ensino Superior foram utilizadas para coleta de dados. A consistência semipastosa do alimento associa-se com o tamanho exagerado do orifício (p<0,05), circunstância de maior frequência (64,20 por cento). Medidas educativas e preventivas devem ser efetuadas precocemente pelos profissionais da área da saúde para que hábitos adequados sejam adquiridos pelos pais ou responsáveis

Development and control of caries lesions on the occlusal surface using a new in vivo caries model

The aim of this study was to develop a new in vivo caries model for the occlusal surface and to describe the enamel features observed before and after dental plaque control (DPC). Four volunteers (12-15 years old) participated in the experiment, each of which was due to have 2 homologous first premolars extracted for orthodontic reasons. Test surfaces did not present visible signs of demineralization, opacities or fillings. A wire mesh was used to promote dental plaque accumulation on the occlusal surface. After 4 weeks, the wire mesh was removed and DPC was performed. In Groups 1 and 2, DPC was performed by the subjects daily and, in Groups 3 and 4, DPC was performed by the subjects daily and by the professional weekly. One tooth/pair of Groups 1 and 3 was extracted after 2 weeks. One tooth/pair of Groups 2 and 4 was extracted after 4 weeks. All test surfaces showed demineralization after the wire mesh was removed. The observed re-establishment of the enamel brightness was directly related to the increase of the DPC duration. In polarized light microscopy, interindividual differences varying from pseudoisotropic areas to enamel lesions were noted in specimens submitted to 2 weeks of DPC. Specimens submitted to 4 weeks of DPC showed less tissue porosity. It was concluded that the new in vivo caries model was effective since all occlusal surfaces presented clinical and microscopic signs of mineral loss in different stages after 4 weeks of cariogenic challenge. After DPC on the test surfaces, there was a reduction of mineral loss suggesting control of demineralization on these surfaces

Determinação da atividade antimicrobiana de soluções utilizadas na higiene bucal de bebês / Determination of the antimicrobial activity of solutions used in infant oral hygiene

O objetivo deste estudo foi avaliar e comparar o efeito antimicrobiano de soluções utilizadas na higiene bucal sobre a microbiota de bebês. Após a coleta de "pool" de saliva não estimulada e placa dental de 20 bebês, foi realizado o teste de difusão em ágar. Através dos resultados obtidos e analisados por Anova e teste de Tukey, verificou-se que as soluções controle, de bicarbonato de sódio e a obtida da infusão de Matricaria chamomilla não apresentaram efeito antimicrobiano, independente da concentração. A solução de H2O2 (3 por cento) e de NaF (0,02 por cento) apresentaram um efeito significativo (p<0,01), sendo que a solução de H2O2 apresentou uma ação superior (p<0,01) à de NaF, independente da origem do inóculo.

Estudo transversal da evoluçäo da dentiçäo decídua: forma dos arcos, da sobressaliência e da sobremordida / Cross-sectional study of the evolution of the primary dentition: shape of dental arches, overjet and overbite

O objetivo deste trabalho foi avaliar as características da dentiçäo decídua de crianças de 06 a 39 meses de idade, matriculadas em quatro creches do município do Rio de Janeiro - Brasil. Foram avaliadas a forma dos arcos dentários, sobressaliência e sobremordida, relacionando-as com gênero e fase de desenvolvimento da dentiçäo decídua Com relaçäo ao arco superior, 68,6 por cento das crianças possuíam arco arredondado e 31,4 por cento forma triangular. Quanto ao arco inferior, 92 por cento o apresentaram em forma de "U" e 8 por cento em forma de quadrado. A sobressaliência moderada ocorreu em 38,3 por cento, enquanto que a leve ocorreu em 30,3 por cento das crianças. A sobremordida exagerada (26,6 por cento) e a negativa (25,5 por cento) foram as mais prevalentes. Näo houve diferença significante entre as freqüências das diferentes formas dos arcos dentários, sobressaliência e sobremordida em relaçäo ao gênero. Houve uma associaçäo estatisticamente significante (Qui quadrado, p<0,001) entre a forma dos arcos superiores, o grau de sobressaliência e o grau de sobremordida em relaçäo à fase de desenvolvimento da dentiçäo. No presente estudo, foi possível observar um aumento significativo das maloclusöes com a erupçäo dos primeiros molares decíduos e elevaçäo da dimensäo posterior. Dessa forma, torna-se extremamente importante que a primeira visita odontológica ocorra no primeiro ano de vida, possibilitando ao odontopediatra a prevençäo ou diagnóstico precoce de maloclusöes na dentiçäo decídua em desenvolvimento

A influência do perfil materno na saúde bucal da criança: relato de caso / The influence of mother's profile on child's oral health: case report

A cárie de estabelecimento precoce tem sido descrita como qualquer tipo de cárie que afete bebês e crianças pré-escolares, na qual existe associaçäo de fatores de risco biológicos e näo-biológicos. Este artigo tem como objetivo relatar, através de um caso clínico de cárie de estabelecimento precoce, a influência do perfil materno na condiçäo bucal de uma criança pré-escolar. Os autores ressaltam que existe uma associaçäo dos diversos fatores etiológicos na ocorrência da doença cárie e que há necessidade de revisäo nos atuais métodos de prevençäo e controle da doença

Hábitos alimentares e prevalência da doença cárie em bebês / Eating habits and dental caries in infants

Este estudo teve como objetivo analisar a correlaçäo entre hábitos alimentares e prevalência da doença cárie em 100 crianças pertencentes a uma instituiçäo pública de ensino com idades entre 0 e 36 meses (média 24 meses), de ambos os sexos. Näo foi demonstrada, estatisticamente, associaçäo entre aleitamento natural e artificial prolongados e ocorrência da doença cárie (p=0,59; p=0,26, respectivamente). Constatou-se uma associaçäo significativa entre consumo de sacorose, refrigerantes e alimentos sólidos cariogênicos com prevalência da doença cárie (p=0,04; p=0,001; p=0,004, respectivamente