[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
Caries Research 01/2013; 47(4):273-283. · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
PLoS ONE 01/2012; 7(9):e45022. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Regarding host aspects, there has been strong evidence for a genetic component in the etiology of caries. The salivary protein lactotransferrin (LTF) exhibits antibacterial activity, but there is no study investigating the association of polymorphisms in the promoter region of LTF gene with caries. The objective of this study was firstly to search the promoter region of the human LTF gene for variations and, if existent, to investigate the association of the identified polymorphisms with dental caries in 12-year-old students. From 687 unrelated, 12-year-old, both sex students, 50 individuals were selected and divided into two groups of extreme phenotypes according to caries experience: 25 students without (DMFT = 0) and 25 with caries experience (DMFT ≥ 4). The selection of individuals with extreme phenotypes augments the chances to find gene variations which could be associated with such phenotypes. LTF gene-putative promoter region (+39 to -1143) of the selected 50 individuals was analyzed by high-resolution melting technique. Fifteen students, 8 without (DMFT = 0) and 7 with caries experience (mean DMFT = 6.28), presented deviations of the pattern curve suggestive of gene variations and were sequenced. However, no polymorphisms were identified in the putative promoter region of the LTF gene.
International Journal of Dentistry 01/2011; 2011:571726.
[Show abstract][Hide abstract] ABSTRACT: The present study evaluated the association between lactotransferrin (LTF) gene polymorphism (exon 2, A/G, Lys/Arg) and dental caries.
A convenience sample of 110 individuals, 12 years old, was divided into: group 1, 48 individuals without caries experience (DMFT=0), and group 2, 62 subjects with caries experience (DMFT>or=1). DNA was obtained from a mouthwash with 3% glucose solution, followed by a scrapping of the oral mucosa. After DNA purification, polymerase chain reaction (PCR), single strand conformation polymorphism (SSCP) was performed to access the study polymorphism. The LTF A/G (Lys/Arg) polymorphism had been previously reported as located in exon 1.
Allele 1 of the study polymorphism was associated with low DMFT index and showed a protective effect against caries experience (OR=0.16, IC=0.03-0.76, p=0.01).
Lactotransferrin A/G (exon 2, Lys/Arg) polymorphism was associated with susceptibility to dental caries in 12-year-old students.
Journal of applied oral science: revista FOB 04/2010; 18(2):166-70. · 0.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aiming to contribute to the study of mechanisms involved in the anticariogenic properties of dental materials, this study assessed the suitability of a short-term in situ model to evaluate the anticariogenic potential of ionomeric materials.
The study used a 3-phase crossover, double blind design, and in each phase eight volunteers wore palatal appliances containing four enamel blocks restored with one of the following materials: composite resin (CR-Z250) (negative control), a conventional glass ionomer cement (GIC-Ketac-Fil) or a resin-modified GIC (RM-GIC-Vitremer). The restored blocks were covered with a "test plaque" of S. mutans, placed in palatal appliances and a cariogenic challenge was made during 1 min with 20% sucrose solution. After 45 min, test plaque was collected for fluoride (F) analysis. Enamel surface microhardness was previously determined at one side of the restoration and the percentage of surface microhardness change (%SMC) in relation to baseline (other side) was calculated. F concentration in enamel was also evaluated.
Split-plot ANOVA showed a statistically lower %SMC on enamel around the ionomeric materials than around the CR (p<0.05). This result was supported by a statistically higher F concentration in test plaque (P<0.001) and in enamel (P<0.001) restored with the ionomeric materials when compared to the CR.
The results suggest that the short-term in situ model tested is useful for studying the anticariogenic potential of dental materials that release fluoride.
Journal of Dentistry 07/2005; 33(6):491-7. · 3.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the effect of sealants on enamel demineralization, focusing on physical protection of the sealed enamel and fluoride protection of the adjacent unsealed enamel. Occlusal fissures with areas measuring 12 mm2 were delimited in 48 extracted molars, randomly divided into 4 groups (n =12): 1) no sealing; 2) sealing with a resin-modified glass-ionomer (Vitremer, 3M ESPE); 3) sealing with a fluoride-releasing composite sealant (Clinpro Sealant, 3M ESPE); and 4) sealing with a non-fluoridated composite sealant (Concise, 3M ESPE). A 4-mm2 window was outlined on the buccal enamel for analysis of fluoride uptake. Following treatment, groups 2, 3 and 4 were subjected to 5-days of pH-cycling, while group 1 was kept in a moist environment at 37 degrees C. Fluoride uptake was assessed by dental biopsy, and the amount of fluoride released to the cycling solutions was determined by ion analysis. Enamel demineralization around the sealants was evaluated by cross-sectional micro-hardness analysis. Group 2 showed higher levels of fluoride release (P < 0.01) and uptake by enamel (P < 0.05), and lower levels of demineralization (P < 0.05) than groups 3 and 4. Group 3 exhibited reduced demineralization on unsealed enamel and provided fluoride uptake in a distant enamel area, while group 4 did not.
[Show abstract][Hide abstract] ABSTRACT: Since the effect of iron (Fe) on the cariogenicity of sucrose in humans is unexplored, this study assessed in situ the effect of Fe co-crystallized with sucrose (Fe-sucrose) topically applied in vitro on the acidogenicity, biochemical and microbiological composition of the dental biofilm formed in vivo and on the demineralization of the enamel. During two phases of 14 days each, 16 volunteers wore palatal appliances containing blocks of human enamel, which were submitted to four groups of separate treatments: (1) water; (2) 20% sucrose; (3) 20% (w/v) sucrose plus 18 microg Fe/ml, and (4) 20% (w/v) sucrose plus 70 microg Fe/ml. The solutions were dripped onto the blocks 8 times per day. The biofilms formed on the blocks were analyzed with respect to acidogenicity, biochemical and microbiological composition. Mineral loss was determined on enamel by surface and cross-sectional microhardness. Lower demineralization was found in the blocks subjected to Fe-sucrose (70 microg Fe/ml) than in those treated with sucrose (p < 0.05). This concentration of Fe also reduced significantly the populations of mutans streptococci in the biofilm formed on the blocks. In conclusion, our data suggest that Fe may reduce in situ the cariogenic potential of sucrose and the effect seems to be related to the reduction in the populations of mutans streptococci in the dental biofilm formed.
Caries Research 01/2005; 39(2):123-9. · 2.51 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study describes dental caries data and fluorosis in seven municipalities in the Sorocaba region, S o Paulo State, Brazil, comparing those with fluoridated as opposed to non-fluoridated water. Criteria were those proposed by the World Health Organization (WHO, 1997), adapted by the School of Public Health, University of S o Paulo. The sample was selected at random, without replacement, and was calculated by age, accepting a design error of 2 and a sampling loss of 20% (n = 96 per age). There were six trained examiners, with accepted agreement percentage above 89% for all variables. In the Sorocaba region, the dmft index in 5 year-old children was 3.1, and 37.6% were caries-free (DMFT = 0). At age 12, 32.3% were caries-free (DMFT = 0), and the DMFT index in the region was 2.6, thus characterizing the area as having a low prevalence of caries. In areas with fluoridated water, the proportion of caries-free children at 12 years was higher than in those without fluoridated water (p = 0.019), and the DMFT was lower (p = 0.001). Prevalence of fluorosis at age 12 was 12.7% in the Sorocaba area and did not pose a public health problem according to the community fluorosis index (CFI).
Cadernos de Saúde Pública 01/2003; 19(4):1063-71. · 0.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: The aim of this study was to compare socioeconomic aspects, oral health habits and salivary parameters between 12-year-old students with and without caries experience. MATERIAL AND METHODS: A sample of 113 non-related 12-year-old subjects was selected in a private school of Curitiba-PR, Brazil, for a case-control study. They were divided into groups with and without caries experience through the DMFT index. The frequency of tooth brushing, use of dental floss, diet, frequency of dentist visit, fluoride use, dental plaque index, socioeconomic aspects and salivary parameters were evaluated. Data were analyzed by qui-square and Mann-Whitney. RESULTS: Results showed no statistical difference between the groups in relation to oral hygiene habits and socioeconomic status. It was observed an association between dental plaque presence and caries experience, although not significant (p = 0.08). A reduced salivary flow was highly associated with decay experience (p = 0.00). CONCLUSION: It was concluded that the salivary flow was an important factor to determine dental caries experience in a homogeneous group of children from a private school of Curitiba-PR. Studies on host response aspects may be desirable in this kind of populations.
Rev. de Clin. Pesq. Odontol.; Vol. 2, No. 1, 2005.