ABSTRACT
The identification of clinical patterns of tooth agenesis in individuals born with craniofacial deformities may be a useful tool for risk determination of these defects. We hypothesize that specific craniofacial deformities are associated with third molar agenesis. OBJECTIVE: The aim of this study was to identify if third molar agenesis could have a relation with other craniofacial structure alterations, such as cleft lip and palate, skeletal malocclusion, or specific growth patterns in humans. DESIGN: Data were obtained from 550 individuals ascertained as part of studies aiming to identify genetic contributions to oral clefts. 831 dental records of patients aged over eight years seeking orthodontic treatment were also included. SN-GoGn angle were used to classify the growth pattern (hypo-divergent, normal and hyper-divergent), and the ANB angle was used to verify the skeletal malocclusion pattern (Class I, II and III). Panoramic radiographs were used to determine third molar agenesis. RESULTS: A high frequency of third molar agenesis among individuals born with cleft lip with or without cleft palate (55%), as well as among their relatives (93.5%) was found. Third molar agenesis was not associated to skeletal malocclusion or growth pattern. CONCLUSION: It appears that third molar agenesis is associated with the disturbances that lead to cleft lip and palate.
Subject(s)
Anodontia/complications , Anodontia/epidemiology , Craniofacial Abnormalities/complications , Craniofacial Abnormalities/ethnology , Molar, Third/abnormalities , Abnormalities, Multiple/epidemiology , Adolescent , Adult , Biomarkers , Child , Cleft Lip/epidemiology , Cleft Lip/ethnology , Cleft Lip/genetics , Cleft Palate/epidemiology , Female , Humans , Male , Malocclusion/classification , Malocclusion/etiology , Mandible/abnormalities , Mandible/pathology , Maxilla/abnormalities , Maxilla/pathology , Orthodontics , Phenotype , Prospective Studies , Radiography, Panoramic , Young AdultABSTRACT
Caries is the most common chronic, multifactorial disease in the world today; and little is still known about the genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified five loci related to caries susceptibility: 5q13.3, 13q31.1, 14q11.2, 14q 24.3, and Xq27. In the present study, we fine mapped the 14q11.2 locus to identify genetic contributors to caries susceptibility. Four hundred seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. An additional 387 DNA samples from unrelated individuals were used to determine allele frequencies. For replication purposes, a total of 1,446 independent subjects from four different populations were analyzed based on their caries experience (low versus high). Forty-eight markers in 14q11.2 were genotyped using TaqMan chemistry. Transmission disequilibrium test was used to detect over transmission of alleles in the Filipino families, and Chi-square, Fisher's exact and logistic regression were used to test for association between low caries experience and variant alleles in the replication data sets. We finally assessed the mRNA expression of TRAV4 in the saliva of 143 study subjects. In the Filipino families, statistically significant associations were found between low caries experience and markers in TRAV4. We were able to replicate these results in the populations studied that were characteristically from underserved areas. Direct sequencing of 22 subjects carrying the associated alleles detects one missense mutation (Y30R) that is predicted to be probably damaging. Finally, we observed higher expression in children and teenagers with low caries experience, correlating with specific alleles in TRAV4. Our results suggest that TRAV4 may have a role in protecting against caries.
Subject(s)
Chromosomes, Human, Pair 14/genetics , Dental Caries/epidemiology , Dental Caries/genetics , Genes, T-Cell Receptor alpha/genetics , Genetic Predisposition to Disease/genetics , Base Sequence , DNA Primers/genetics , Gene Frequency , Genetic Association Studies , Genetic Loci/genetics , Humans , Inheritance Patterns/genetics , Linkage Disequilibrium , Logistic Models , Molecular Sequence Data , Mutation, Missense/genetics , Philippines/epidemiology , Saliva/metabolism , Sequence Analysis, DNAABSTRACT
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.
