Adriana Modesto

Interferon regulatory factor 6 (IRF6) and fibroblast growth factor receptor 1 (FGFR1) contribute to human tooth agenesis.

Phenotypic characteristics expressed in syndromes give clues to the factors involved in the cause of isolated forms of the same defects. We investigated two genes responsible for craniofacial syndromes, FGFR1 and IRF6, in a collection of families with isolated tooth agenesis. Cheek swab samples were obtained for DNA analysis from 116 case/parent trios. Probands had at least one developmentally missing tooth, excluding third molars. In addition, we studied 89 cases and 50 controls from Ohio to replicate any positive findings. Genotyping was performed by kinetic polymerase chain‐reaction or TaqMan assays. Linkage disequilibrium analysis and transmission distortion of the marker alleles were performed. The same variants in the IRF6 gene that are associated with isolated orofacial clefts are also associated with human tooth agenesis (rs861019, P = 0.058; rs17015215—V274I, P = 0.0006; rs7802, P = 0.004). Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes. The craniofacial phenotypic characteristics of these syndromes include oral clefts and preferential tooth agenesis of incisors and premolars, besides pits on the lower lips. Also it appears that preferential premolar agenesis is associated with FGFR1 (P = 0.014) and IRF6 (P = 0.002) markers. There were statistically significant data suggesting that IRF6 interacts not only with MSX1 (P = 0.001), but also with TGFA (P = 0.03).

Axis inhibition protein 2 (AXIN2) polymorphisms and tooth agenesis

Tooth agenesis is a common congenital disorder that affects almost 20% of the worlds population. A number of different genes have been shown to be associated with cases of tooth agenesis including AXIN2, IRF6, FGFR1, MSX1, PAX9, and TGFA. Of particular interest is AXIN2, which was linked to two families segregating oligodontia and colorectal cancer. We studied two collections of families affected with tooth agenesis and tested them for association with AXIN2. Significant association between tooth agenesis and AXIN2 was found (p=0.02) in cases with at least one missing incisor. Our work further supports a role of AXIN2 in human tooth agenesis and for the first time suggests AXIN2 is involved in sporadic forms of common incisor agenesis. Future studies should identify which specific tooth agenesis sub-phenotypes are consequence of AXIN2 genetic variations. A sub-set of these cases could have an increased susceptibility for colon cancer or other types of tumours and this knowledge would have significant clinical implications.

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.

Caries: review of human genetics research.

The NIH Consensus Development Program released a statement in 2001 (http://consensus.nih.gov/2001/2001DentalCaries115html.htm) and listed six major clinical caries research directions. One of these directions was the need for genetic studies to identify genes and genetic markers of diagnostic, prognostic and therapeutic value. This last decade has seen a steep increase in studies investigating the presence of genetic factors influencing individual susceptibility to caries. This review revisits recent caries human genetic studies and provides a perspective for future studies in order to fulfil their promise of revolutionizing our understanding of and the standard of care for the most prevalent bacteria-mediated non-contagious disease in the world.

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.

Prevalence of dental trauma in Pan American Games athletes

The aim of this cross-sectional epidemiological survey was to assess the prevalence of dental trauma in athletes representing 42 countries competing at the most recent Pan American Games (XV Pan Am) held in Rio de Janeiro, Brazil in July of 2007, and to determine prior use and type of mouthguard among this group of athletes. The examiners participated in standardization and calibration training sessions before the field phase began. Invitations were sent to >5500 participating athletes competing in 41 sports and to the Medical Committee of the Pan American Sports Organization before and during the XV PAN. A convenience sample of 409 athletes was recruited. After signing an informed consent, all athletes answered a questionnaire. Data were collected at the clinical examination and recorded on a specific trauma form. The mean age of the athletes was 24.4 +/- 5.3 years. Males comprised 55% of the sample; females 45%. The prevalence of dental trauma among the athletes was 49.6% (n = 203) with no gender-based differences. Most of these injuries (63.6%) were related to activities during training or competition. Sports with the highest injury prevalence were wrestling (83.3%), boxing (73.7%), basketball (70.6%) and karate (60%). The most common injury was enamel fracture (39.8%); root fracture was the least common (0.4%). The teeth most affected were the maxillary permanent central incisors (n = 113), followed by the mandibular central incisors (n = 19). Based on the results of this study, nearly one-half of the subjects had experienced previous dental trauma; the majority related to sports activities. Furthermore, only 17% of the athletes reported prior mouthguard use; the most frequent mouthguards reported were boil-and-bite. These results suggest the importance of enhanced educational efforts and the use of properly fitted mouthguards to reduce dental trauma among athletes in international sports competition, especially in sports where mouthguards are not mandatory.

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.

Antimicrobial effects of the combination of chlorhexidine and xylitol

Aims To assess the effect of combining 1% chlorhexidine varnish (CHX) with xylitol chewing gum (XYL) on Streptococcus mutans and biofilm levels in 6-8-year-old children.Design Randomised controlled study.Subjects and methods Eighty-two 6-8-year-old children were randomly divided into groups as follows: G1 (n = 20): xylitol chewing gum twice a day after breakfast and lunch; G2 (n = 20): xylitol gum as G1 plus chlorhexidine varnish application at the start of the study and after one and two months; G3 (n = 20): chlorhexidine varnish as G2; and G4 (n = 22): fluoride gel application at the start of the study and after one and two months. Microbiological tests were performed to assess Streptococcus mutans colony forming units (CFU) and the teeth of those children with moderate or higher CFU scores were examined for visible biofilm. CFU scores were categorised as follows: 0 = absence of S. mutans, 1 = low level (1-10 CFU), 2 = moderate level (11-100 CFU), 3 = high level (101-250 CFU), 4 = very high level (>250 CFU). Biofilm scores based on a scale from 0 (absence of biofilm) to 5 (thick biofilm firmly adhered to posterior and anterior teeth) were obtained.Results The biofilm reduction was greater in G2 and G3, with mean values of 3.38 and 3.17 to 1.79 and 1.88, respectively (p <0.05). All groups presented a reduction in the S. mutans levels. XYL + CHX showed the largest reduction throughout the study period, with 58.3% in the first month, 84.2% in the second and 92.9% at the end of the study.Conclusions The XYL + CHX combination was efficient and superior to single treatments in controlling biofilm and suppressing S. mutans.

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.

Detection of Streptococcus mutans Genomic DNA in Human DNA Samples Extracted from Saliva and Blood

Caries is a multifactorial disease, and studies aiming to unravel the factors modulating its etiology must consider all known predisposing factors. One major factor is bacterial colonization, and Streptococcus mutans is the main microorganism associated with the initiation of the disease. In our studies, we have access to DNA samples extracted from human saliva and blood. In this report, we tested a real-time PCR assay developed to detect copies of genomic DNA from Streptococcus mutans in 1,424 DNA samples from humans. Our results suggest that we can determine the presence of genomic DNA copies of Streptococcus mutans in both DNA samples from caries-free and caries-affected individuals. However, we were not able to detect the presence of genomic DNA copies of Streptococcus mutans in any DNA samples extracted from peripheral blood, which suggests the assay may not be sensitive enough for this goal. Values of the threshold cycle of the real-time PCR reaction correlate with higher levels of caries experience in children, but this correlation could not be detected for adults.