[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.
Human Genetics 05/2013; 132(9). DOI:10.1007/s00439-013-1313-4 · 4.82 Impact Factor
[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. DOI:10.1159/000346278 · 2.28 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 09/2012; 7(9):e45022. DOI:10.1371/journal.pone.0045022 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective: Dental caries is a common multifactorial disease, resulting from the interaction of biofilm, cariogenic diet and host response over time. Lactotransferrin (LTF) is a main salivary glycoprotein, which modulates host immune-inflammatory and antibacterial response. Although a genetic component for caries outcome has been identified, little is known over genetic aspects underlying its susceptibility. Thus, the aim of this study was to investigate the association between LTF gene polymorphisms and dental caries.
Method: A total of 677 12-yr-old students were selected from Curitiba (PR), Brazil, 6 public and 6 private schools: 346 with (DMFT≥1) and 331 without caries experience (DMFT=0). Also, individuals concentrating higher levels of disease (polarization group, DMFT≥2, n=253) were tested against those with DMFT≤1 (n=424), (mean DMFT=1,23 in Curitiba). Along with clinical parameters (fluorosis, salivary flow, buffer capacity, gingivitis, and presence of plaque), LTF tag SNPs (rs11716497, rs2073495, and rs6441989) were analyzed using univariate analysis and multivariate logistic regression model (p<0.05).
Result: Allele A for tag SNP rs6441989 was found to be significantly less frequent in the polarization group, conferring a protective effect against caries experience [AA+AG x GG (OR: 0.710, CI: 0.514-0.980, p=0.045)], which remained significantly associated with caries protection in the presence of gingivitis (p=0.020) and plaque (p=0.035).
Conclusion: Allele A for polymorphism rs6441989 of LTF gene was associated with protection against dental caries in the presence of clinical variables such as gingivitis and plaque. Saliva is one of the host factors that interact with the biofilm, avoiding enamel demineralization caused by acids resulting from cariogenic bacteria metabolism. Therefore, the identification of salivary factors polymorphisms involved with caries development might contribute for the unveiling towards caries genetic background.
[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 12/2011; 2011(6):571726. DOI:10.1155/2011/571726
[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. DOI:10.1590/S1678-77572010000200011 · 0.92 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.