Marcelo de Castro Costa

Enamel Formation Genes Influence Enamel Microhardness Before and After Cariogenic Challenge

There is evidence for a genetic component in caries susceptibility, and studies in humans have suggested that variation in enamel formation genes may contribute to caries. For the present study, we used DNA samples collected from 1,831 individuals from various population data sets. Single nucleotide polymorphism markers were genotyped in selected genes (ameloblastin, amelogenin, enamelin, tuftelin, and tuftelin interacting protein 11) that influence enamel formation. Allele and genotype frequencies were compared between groups with distinct caries experience. Associations with caries experience can be detected but they are not necessarily replicated in all population groups and the most expressive results was for a marker in AMELX (p = 0.0007). To help interpret these results, we evaluated if enamel microhardness changes under simulated cariogenic challenges are associated with genetic variations in these same genes. After creating an artificial caries lesion, associations could be seen between genetic variation in TUFT1 (p = 0.006) and TUIP11 (p = 0.0006) with enamel microhardness. Our results suggest that the influence of genetic variation of enamel formation genes may influence the dynamic interactions between the enamel surface and the oral cavity.

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.

Genetic variation in MMP20 contributes to higher caries experience

UNLABELLED Matrix metalloproteinases play an important role during the initial process of enamel development and therefore may play a role in caries. OBJECTIVES To evaluate the association between MMP20 and caries experience in Brazilian children. METHODS Eligible unrelated children with or without caries were evaluated using a cohort design. Demographic data and oral health habits were obtained though a questionnaire. Caries data was collected by clinical examination. Genotyping of the selected polymorphism was carried out by real-time PCR from genomic DNA. Allele and genotype frequencies were compared between groups with distinct caries experience and oral health habits. RESULTS Of 388 subjects, 161 were caries free children. There were no differences between caries levels and genotype distribution in the total cohort. When ethnic background was considered, differences in genotype distribution were observed in caries free children vs. children with caries in Caucasians (p=0.03). Differences could also be seen when poor oral hygiene was used to stratify the analysis (p=0.02). Regression analysis, adjusted for genotype and ethnicity, confirmed that ingestion of sweets between meals increases the risk of presenting carious lesions (p=0.00001; OR=2.33; 95%CI 1.53-3.54). CONCLUSION Variation in MMP20 may be associated with caries experience mainly in Caucasian subjects with poor oral health habits.

Prevalence of Dental Anomalies in Nonsyndromic Individuals With Cleft Lip and Palate: A Systematic Review and Meta-analysis

Objective To assess whether individuals born with nonsyndromic oral clefts display a higher frequency of dental anomalies. Design A search of MEDLINE, BIREME, OVID ALL EMB Reviews, and The Cochrane Library was conducted. The methodologic quality of the papers selected was assessed and scored. Papers reporting observational controlled studies of nonsyndromic forms of oral cleft matched for dental anomalies in primary and/or permanent teeth were included without language restrictions. Eligible studies were scored as “A”—low risk of bias, “B”—moderate risk of bias, or “C”—high risk of bias and poor quality. Fixed and random effects models were used to aggregate individual odds ratios (OR) and to derive pooled estimates and 95% confidence intervals. Results Six studies fulfilled our selection criteria and were included in the meta-analysis. Three distinct subgroup analyses were carried out in terms of dental anomalies. In the tooth agenesis meta-analysis, a random effects model was used because of heterogeneity and showed a significant association between tooth agenesis and oral clefts (OR = 12.31; 95% confidence interval [CI] = 3.75 to 40.36). In the remaining analyses, the fixed effects model revealed a positive association between supernumerary (OR = 4.99; 95% CI, 2.58 to 9.64) and crown morphologic abnormalities (OR = 5.69; 95% CI, 3.96 to 8.19) with oral clefts. Most included studies were of low to moderate quality. Conclusion Although general limitations in study design were observed, the evidence suggests that a higher number of dental anomalies in the permanent dentition are noted in individuals born with oral clefts.

MMP13 polymorphism decreases risk for dental caries.

Recent evidence suggests that genetic studies may contribute to a better understanding of individual susceptibility to caries. Matrix metalloproteinases (MMPs) and their tissue inhibitors have been suggested to be involved in the caries process. The purpose of this study was to determine if polymorphisms in MMP2 (rs243865), MMP9 (rs17576), MMP13 (rs2252070), and TIMP2 (rs7501477) were associated with caries. Eligible unrelated children and adolescents were evaluated using a cross-sectional design. Data on oral health habits was obtained through a questionnaire and caries data was collected by clinical examination. Genotyping of the selected polymorphisms was carried out by real-time PCR. Allele and genotype frequencies were compared between individuals with and without caries experience. Of 505 subjects, 212 were caries-free and most subjects (61.2%) had mixed dentition. Allele frequency of MMP2, MMP13 and TIMP2 was different between caries-affected and caries-free individuals, with significant association for MMP13 (p = 0.004). Mutant allele carriers for MMP13 demonstrated a significantly decreased risk for caries (OR = 0.538, 95% CI 0.313–0.926); this result remained significant after adjustment for candidate genes, type of dentition and dietary factors. Allelic and genotype frequencies of the polymorphism in MMP9 were similar in caries-affected and caries-free individuals. Genetic variations in MMP13 may contribute to individual differences in caries susceptibility. Our findings reinforce that susceptibility to caries results from gene-environment interactions.

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.

Supernumerary teeth vary depending on gender

The presence of supernumerary teeth (ST) is a dental developmental anomaly of patterning and morphogenesis. Its variability of morphology, location and developmental timing can shed light on its etiology. In this work we report ST patterns. Orthopantomograms of 1,166 pediatric subjects were examined and the morphology, location and timing of the formation of ST were determined. The frequency of supernumerary teeth in the studied population was 2.3% (n = 27). Twenty-five subjects presented one ST. Maxilla midline was the most commonly affected region (nine cases). We noted high incidence of conical morphology in the midline region. Only teeth with tuberculate morphology presented delayed formation. ST in the midline region occurred more often in males whereas ST in the incisor region were more common in females. In conclusion, ST patterns vary depending on gender.

Fine-Mapping of 5q12.1-13.3 Unveils New Genetic Contributors to Caries

Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified the interval 5q12.1–5q13.3 as linked to low caries susceptibility in Filipino families. Here we fine-mapped this region in order to identify genetic contributors to caries susceptibility. Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT scores and genotype data of 75 single-nucleotide polymorphisms were evaluated in the Filipino families with the Family-Based Association Test. For replication purposes, a total 1,467 independent subjects from five different populations were analyzed in a case-control format. In the Filipino cohort, statistically significant and borderline associations were found between low caries experience and four genes spanning 13 million base pairs (PART1, ZSWIM6, CCNB1, and BTF3). We were able to replicate these results in some of the populations studied. We detected PART1 and BTF3 expression in whole saliva, and the expression of BTF3 was associated with caries experience. Our results suggest BTF3 may have a functional role in protecting against caries.

MMP1 and MMP20 contribute to tooth agenesis in humans

OBJECTIVE Variations in genes that are critical for tooth formation may contribute to the tooth agenesis. MMPs are potential candidate genes for dental alterations based on the roles they play during embryogenesis. The aim of this study was to investigate the possible association between MMP1, MMP3, and MMP20 and tooth agenesis. METHODS One hundred sixty-seven nuclear families from two different populations were analysed, 116 from Brazil and 51 from Turkey. Probands had at least one congenitally missing tooth. DNA samples were obtained from blood or saliva samples and genotyping was performed using TaqMan chemistry. In addition, Mmp20 was selected for quantitative real-time polymerase chain reaction analysis with SYBR Green I Dye in mouse tooth development. RESULTS Associations between tooth agenesis and MMP1 (p=0.007), and MMP20 (p=0.03) were found in Brazilian families. In the total dataset, MMP20 continued to be associated with tooth agenesis (p=0.01). Mmp20 was not expressed during the initial stages of tooth development. CONCLUSION Our findings provide evidence that MMP1 and MMP20 play a role in human tooth agenesis.

Genetic influences on dental enamel that impact caries differ between the primary and permanent dentitions

Clinically, primary and permanent teeth are distinct anatomically and the presentation of caries lesions differs between the two dentitions. Hence, the possibility exists that genetic contributions to tooth formation of the two dentitions are different. The purpose of this study was to test the hypothesis that genetic associations with an artificial caries model will not be the same between primary and permanent dentitions. Enamel samples from primary and permanent teeth were tested for microhardness at baseline, after carious lesion creation, and after fluoride application to verify association with genetic variants of selected genes. Associations were found between genetic variants of ameloblastin, amelogenin, enamelin, tuftelin, tuftelin interactive protein 11, and matrix metallopeptidase 20 and enamel from permanent teeth but not with enamel from primary teeth. In conclusion, our data continue to support that genetic variation may impact enamel development and consequently individual caries susceptibility. These effects may be distinct between primary and permanent dentitions.