There is evidence for a genetic component in caries susceptibility, and studies in humans have suggested that variation in enamel formation genes and their interaction with Streptococcus mutans levels may contribute to caries. For the present study, we used DNA samples collected from 173 unrelated children from Istanbul: 91 children with 4 or more affected tooth surfaces and 82 caries-free children. Six single-nucleotide polymorphism markers were genotyped in selected candidate genes (ameloblastin, amelogenin, enamelin, tuftelin 1 and tuftelin interacting protein 11) that influence enamel formation. Allele and genotype frequencies were compared between groups with distinct caries experience. Regression analysis was used for the evaluation of individual gene effects, environmental effects and gene-environment interactions. Overrepresentation of the C allele of the amelogenin marker was seen in cases with dmft scores higher than 8 (p = 0.01) when compared to controls. Also, overrepresentation of the T allele of the ameloblastin marker was seen in cases with dmfs scores higher than 10 (p = 0.05) when compared to controls. In addition, the CT genotype of the tuftelin rs3790506 marker was overrepresented in cases with dmft scores higher than 5 (p = 0.05) and dmfs scores higher than 6 (p = 0.05) compared to controls. The best-fitting model showed that dmfs is increased when the following factors are present: (1) females and both the anterior and posterior teeth are affected simultaneously, (2) when the T allele of the tuftelin rs3790506 is involved, and (3) the C allele of the amelogenin rs17878486 is involved. Our study provides support that genes involved in enamel formation modify caries susceptibility in humans.

Genetic disturbances during dental development influence variation of number and shape of the dentition. In this study, we tested if genetic variation in enamel formation genes is associated with molar-incisor hypomineralization (MIH), also taking into consideration caries experience. DNA samples from 163 cases with MIH and 82 unaffected controls from Turkey, and 71 cases with MIH and 89 unaffected controls from Brazil were studied. Eleven markers in five genes [ameloblastin (AMBN), amelogenin (AMELX), enamelin (ENAM), tuftelin (TUFT1), and tuftelin-interacting protein 11 (TFIP11)] were genotyped by the TaqMan method. Chi-square was used to compare allele and genotype frequencies between cases with MIH and controls. In the Brazilian data, distinct caries experience within the MIH group was also tested for association with genetic variation in enamel formation genes. The ENAM rs3796704 marker was associated with MIH in both populations (Brazil: p=0.03; OR=0.28; 95% C.I.=0.06–1.0; Turkey: p=1.22e–012; OR=17.36; 95% C.I.=5.98–56.78). Associations between TFIP11 (p=0.02), ENAM (p=0.00001), and AMELX (p=0.01) could be seen with caries independent of having MIH or genomic DNA copies of Streptococcus mutans detected by real time PCR in the Brazilian sample. Several genes involved in enamel formation appear to contribute to MIH.

There is evidence for a genetic component in caries susceptibility, but the disease is greatly influenced by environmental factors, which are extremely difficult to control in humans. For the present study, we used DNA samples collected from 110 unrelated, non-cleft individuals older than 12 years of age from Tiquisate, Guatemala: a population with similar cultural, dietary and hygiene habits, similar access to the dentist and fluoride exposure. Forty-four individuals were designated ‘very low caries experience’ (DMFT ≤2), and 66 were designated ‘higher caries experience’ (DMFT ≧3). Single-nucleotide polymorphism markers were genotyped in selected candidate genes (ameloblastin, amelogenin, enamelin, tuftelin-1, and tuftelin interacting protein 11) that influence enamel formation. Having at least one copy of the rare amelogenin marker allele was associated with increased age-adjusted caries experience. This association was stronger in individuals with higher DMFT (DMFT ≧20; p = 0.0000001). Our results suggest that variation in amelogenin may contribute to caries susceptibility in the population studied. The approach of comparing individuals with extremely distinct caries experiences could be valuable for decreasing the potential influence of environmental factors on genetic studies of caries.

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.

Introduction Several candidate loci have been suggested as influencing mandibular prognathism (1p22.1, 1p22.2, 1p36, 3q26.2, 5p13-p12, 6q25, 11q22.2-q22.3, 12q23, 12q13.13, and 19p13.2). The goal of this study was to replicate these results in a well-characterized homogeneous sample set. Methods Thirty-three single nucleotide polymorphisms spanning all candidate regions were studied in 44 prognathic and 35 Class I subjects from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository. The 44 mandibular prognathism subjects had an average age of 18.4 years, 31 were females and 13 males, and 24 were White, 15 African American, two Hispanic, and three Asian. The 35 Class I subjects had an average age of 17.6 years, 27 were females and 9 males, and 27 were White, six African Americans, one Hispanic, and two Asian. Skeletal mandibular prognathism diagnosis included cephalometric values indicative of Class III such as ANB smaller than two degrees, negative Witts appraisal, and positive A–B plane. Additional mandibular prognathism criteria included negative OJ and visually prognathic (concave) profile as determined by the subject's clinical evaluation. Orthognathic subjects without jaw deformations were used as a comparison group. Mandibular prognathism and orthognathic subjects were matched based on race, sex and age. Genetic markers were tested by polymerase chain reaction using TaqMan chemistry. Chi-square and Fisher exact tests were used to determine overrepresentation of marker allele with alpha of 0.05. Results An association was unveiled between a marker in MYO1H (rs10850110) and the mandibular prognathism phenotype (p=0.03). MYO1H is a Class-I myosin that is in a different protein group than the myosin isoforms of muscle sarcomeres, which are the basis of skeletal muscle fiber typing. Class I myosins are necessary for cell motility, phagocytosis and vesicle transport. Conclusions More strict clinical definitions may increase homogeneity and aid the studies of genetic susceptibility to malocclusions. We provide evidence that MYO1H may contribute to mandibular prognathism.