Dental caries prevalence and severity positively associate with AMY1 gene copy number.

OBJECTIVE: To establish the possible relation between total caries (TC) and caries severity (CS) with the AMY1 gene copy number (AMY1GCN). MATERIALS AND METHODS: This was an observational, cross-sectional, population-based, and association study with 303 participants. Each participant underwent a complete anamnesis and stomatological check-up, and peripheral blood was obtained to extract gDNA. TC and CS were determined as the number of caries at the dental exploration and the number of dental surfaces affected by caries, respectively, and AMY1GCN was determined by qPCR. RESULTS: We found an elevated caries prevalence (92.7%); TC and CS were 8 ± 10 and 10 ± 13 (median ± IR). There were higher TC and CS in those participants with AMY1GCN above the mean value (0.02 and 0.01 p values, respectively). A positive correlation between TC and CS with AMY1GCN (0.11 and 0.125 r values, 0.03 and 0.01 p values, respectively) was found, in addition to an association between TC and CS with AMY1GCN (1.5 and 1.6 OR values, 0.48 and 0.26 p values, respectively). CONCLUSION: TC and CS were positively related to the AMY1GCN. CLINICAL RELEVANCE: Dental caries has a high prevalence and a multifactorial etiology and has been related to a genetic component. Indeed, the salivary enzyme alpha-amylase could play a significant role in caries susceptibility, considering that its codifying gene (AMY1) can show variation in its gene copy number. This can be considered an important factor for the development of caries at a genetic level.

Sweet Taste Receptor Gene and Caries Trajectory in the Life Course.

This study aims to investigate whether the trajectory of dental caries in the life course is associated with rs307355 (TAS1R3) and rs35874116 (TAS1R2) and if there is an epistatic association between rs307355 (TAS1R3) and rs35874116 (TAS1R2). A representative sample of all 5,914 births from the 1982 Pelotas birth cohort was prospectively investigated, and the decayed, missing, and filled teeth (DMF-T) components were assessed at ages 15 (n = 888), 24 (n = 720), and 31 (n = 539) y. Group-based trajectory modeling was used to identify groups with similar trajectories of DMF-T components in the life course. Genetic material was collected, and rs307355 (TAS1R3) and rs35874116 (TAS1R2) were genotyped. Ethnicity was evaluated using ADMIXTURE. Generalized multifactor dimensionality reduction software was used to investigate epistatic interactions. Considering rs307355 (TAS1R3) in the additive effect, the genotype TT was associated with the high decayed trajectory group (odds ratio [OR] = 4.52; 95% confidence interval [CI], 1.15-17.74) and the high missing trajectory group (OR = 3.35; 95% CI, 1.09-10.26). In the dominant effect, the genotype CT/TT was associated with the high decayed trajectory group (OR = 1.64; 95% CI, 1.14-2.35). Allele T was associated with an increased odds of 64% (OR = 1.64; 95% CI, 1.20-2.25) for the decayed component and 41% (OR = 1.41; 95% CI, 1.04-1.92) for the missing component. No associations were observed between rs307355 (TAS1R3) and the filled component. rs35874116 (TAS1R2) was not associated with DMF-T components. Positive epistatic interactions were observed involving rs307355 (TAS1R3) and rs35874116 (TAS1R2) with the decayed component (OR = 1.72; 95% CI, 1.04-2.84). Thus, rs307355 (TAS1R3) genotypes and alleles seem positively associated with the trajectory of decayed and missing components in the life course. Epistatic interaction between rs307355 and rs35874116 may increase the decayed caries trajectory.

An association analysis for genetic factors for dental caries susceptibility in a cohort of Chinese children.

OBJECTIVE: To comprehensively investigate the effects of 25 variants in 15 genes on dental caries susceptibility in a cohort of Chinese children. METHODS: A total of 25 variants in 15 genes were genotyped with MassARRAY iPLEX system and analyzed in 265 healthy controls and 254 children affected by dental caries with different dmft scores. The children with dental caries were stratified into "mild group" (scores from 1 to 3), "moderate group" (scores from 4 to 6), and "severe group" (scores from 7 to 14). RESULTS: The association analysis revealed that rs11362 of defensin ß1 (DEFB1) was significantly associated with dental caries susceptibility (OR = 2.447, p = 1.165E-04). Furthermore, rs11362 was positively correlated with the severity of dental caries. For another selected variant of DEFB1, rs1799946 was significantly associated with dental caries susceptibility in the severe group (OR = 0.473, p = 3.70E-03) and also significant in the group consisted of moderate and severe subjects (OR = 0.623, p = .033). The results from logistic regression in additive, dominant, and recessive models also exhibited the similar patterns. CONCLUSION: Out of 25 selected variants, only 2 of DEFB1 gene (rs11362 and rs1799946) were significantly associated with dental caries susceptibility in children.

FCN1 polymorphisms are not the markers of dental caries susceptibility in Polish children: A case-control study.

OBJECTIVE: To examine the association of four FCN1 SNPs: -542G>A (rs10120023), -144C>A (rs10117466), +6658C>T (rs148649884), and +7895A>G (rs150625869) with dental caries in Polish children. SUBJECTS AND METHODS: The study group consisted of 261 15-year-old Polish teenagers: 82 children with "higher" caries experience (having Decayed Missing Filled Teeth, DMFT >5) and 179 children with "lower" caries experience (having DMFT ≤5). Moreover, in additional comparison, a group of 229 children with caries experience (DMFT ≥1) was compared to a caries-free (DMFT =0) group of 32 children. Extraction of genomic DNA was performed from buccal swabs, and genotyping was performed by Real-Time PCR. RESULTS: FCN1 SNPs +6658C>T and +7895A>G appeared to be monomorphic in our sample. The genotype, allele, or haplotype distributions in FCN1 SNPs -542G>A and -144C>A in children with "higher" caries experience did not differ significantly from those in "lower" caries experience group. Similar results with no significant differences were demonstrated for subjects with DMFT ≥1 compared to subjects with DMFT =0. CONCLUSION: FCN1 SNPs are not the markers of dental caries susceptibility in Polish children.

Classification of caries in third molars on panoramic radiographs using deep learning.

The objective of this study is to assess the classification accuracy of dental caries on panoramic radiographs using deep-learning algorithms. A convolutional neural network (CNN) was trained on a reference data set consisted of 400 cropped panoramic images in the classification of carious lesions in mandibular and maxillary third molars, based on the CNN MobileNet V2. For this pilot study, the trained MobileNet V2 was applied on a test set consisting of 100 cropped PR(s). The classification accuracy and the area-under-the-curve (AUC) were calculated. The proposed method achieved an accuracy of 0.87, a sensitivity of 0.86, a specificity of 0.88 and an AUC of 0.90 for the classification of carious lesions of third molars on PR(s). A high accuracy was achieved in caries classification in third molars based on the MobileNet V2 algorithm as presented. This is beneficial for the further development of a deep-learning based automated third molar removal assessment in future.

Polymorphisms in DSSP (rs36094464) and RUNX2 (rs566712) genes contribute to the susceptibility of dental caries in childhood / Los polimorfismos en los genes DSSP (rs36094464) y RUNX2 (rs566712) contribuyen a la susceptibilidad de la caries dental en la infancia

SUMMARY: Dental caries corresponds to an ecological and non-contagious, dynamic and chronic disease of multifactorial origin; currently there is evidence of how genetic factors could be included as predisposing agents to suffer it, however this evidence is diverse and incipient. a cross-sectional study was p erformed to investigate the possible associations of DSPP (rs36094464), RUNX2 (rs566712) and KLK4 (rs198968) polymorphisms in early childhood caries. Saliva samples of children (2-11years old) were collected and genotyped for DSPP (rs36094464), RUNX2 (rs566712) and KLK4 (rs198968) polymorphisms. Through the ceft index their caries history was determined and the gene variants were students through molecular biology techniques. polymorphisms of the DSSP (rs36094464) and RUNX2 (rs566712) are associated and contribute to the susceptibility of dental caries disease in early childhood, as they are related to their history of caries. KLK4 (rs198968) polymorphisms are not associated. In conclusions, the studied polymorphisms on DSSP and RUNX2 genes are associated with changes in the tooth microarchitecture, favoring the appearance of microlesions that would contribute to dental caries disease susceptibility in early childhood. Also, no association was found for the studied polymorphism of the KLK4 gene with dental caries disease susceptibility.

RESUMEN: La caries dental corresponde a una enfermedad crónica, no contagiosa, dinámica y de origen multifactorial. Actualmente existe evidencia de cómo los factores genéticos podrían incluirse como agentes predisponentes, sin embargo, esta evidencia es diversa e incipiente. Se realizó un estudio transversal para investigar las posibles asociaciones entre los polimorfismos DSPP (rs36094464), RUNX2 (rs566712) y KLK4 (rs198968) y la caries en la infancia. Se colectaron muestras de saliva de niños (de 2 a 11 años de edad) y se genotipificaron para los polimorfismos DSPP (rs36094464), RUNX2 (rs566712) y KLK4 (rs198968). Mediante el índice ceft se determinó su historial de caries y se estudiaron las variantes genéticas mediante técnicas de biología molecular. Los datos obtenidos indican que los polimorfismos del DSSP (rs36094464) y RUNX2 (rs566712) están asociados y contribuyen a la susceptibilidad de la enfermedad de caries dental en la infancia, ya que están - además - relacionados con el historial de caries. En conclusión, los polimorfismos estudiados en los genes DSSP y RUNX2 se asocian a la aparición de microlesiones que contribuirían a la susceptibilidad a la enfermedad de caries dental en la infancia. Creemos que este estudio es importante para la odontopediatría porque destaca el papel de DSSP (rs36094464) y RUNX2 (rs566712) y la susceptibilidad a la caries dental durante la infancia, además resalta la utilidad de la evaluación genética para la predicción y prevención de la caries dental y porque aporta evidencia que indica que los factores genéticos están implicados en la etiología de la caries.

Prediction of Early Childhood Caries Based on Single Nucleotide Polymorphisms Using Neural Networks.

BACKGROUND: Several genes and single nucleotide polymorphisms (SNPs) have been associated with early childhood caries. However, they are highly age- and population-dependent and the majority of existing caries prediction models are based on environmental and behavioral factors only and are scarce in infants. METHODS: We examined 6 novel and previously analyzed 22 SNPs in the cohort of 95 Polish children (48 caries, 47 caries-free) aged 2-3 years. All polymorphisms were genotyped from DNA extracted from oral epithelium samples. We used Fisher's exact test, receiver operator characteristic (ROC) curve and uni-/multi-variable logistic regression to test the association of SNPs with the disease, followed by the neural network (NN) analysis. RESULTS: The logistic regression (LogReg) model showed 90% sensitivity and 96% specificity, overall accuracy of 93% (p < 0.0001), and the area under the curve (AUC) was 0.970 (95% CI: 0.912-0.994; p < 0.0001). We found 90.9-98.4% and 73.6-87.2% prediction accuracy in the test and validation predictions, respectively. The strongest predictors were: AMELX_rs17878486 and TUFT1_rs2337360 (in both LogReg and NN), MMP16_rs1042937 (in NN) and ENAM_rs12640848 (in LogReg). CONCLUSIONS: Neural network prediction model might be a substantial tool for screening/early preventive treatment of patients at high risk of caries development in the early childhood. The knowledge of potential risk status could allow early targeted training in oral hygiene and modifications of eating habits.

Association of LTF, ENAM, and AMELX polymorphisms with dental caries susceptibility: a meta-analysis.

BACKGROUND: This meta-analysis evaluated the association of LTF, ENAM, and AMELX polymorphisms with dental caries susceptibility. METHODS: We searched the Scopus, PubMed/Medline, Web of Science, and Cochrane Library databases to retrieve articles published by October 2019. Review Manager 5.3 software was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs). The results of publication bias tests were retrieved by Comprehensive Meta-Analysis 2.0 software. RESULTS: A total of 150 relevant records were identified; out of which, 16 were entered into the analysis (4 studies assessed LTF, 11 ENAM, and 11 AMELX polymorphisms). Of all polymorphisms, there was a significant association only between ENAM rs3796704 polymorphism and dental caries susceptibility. Both ENAM rs3796704 and AMELX rs17878486 polymorphisms had a significant association with dental caries risk in the Caucasian ethnicity and the studies including caries-free control group. CONCLUSIONS: The results of this meta-analysis showed that the G allele and the GG genotype of ENAM rs3796704 were associated with an increased risk of caries in the case group compared with the control group. But there was no association between LTF rs1126478, ENAM (rs1264848 and rs3796703), and AMELX (rs946252, rs17878486, and rs2106416) polymorphisms and dental caries susceptibility.

Evaluation of the association between tuftelin gene polymorphism, Streptococcus mutans, and dental caries susceptibility.

CONTEXT: Dental caries can be conceptualized as an interaction between genetic and environmental factors. AIMS: The purpose of this study was to identify any polymorphism in tuftelin gene and its association with dental caries susceptibility, either singly or in combination with the microbial causing agent: Streptococcus mutans. SETTINGS AND DESIGN: The presented study included a total of 30 children of age group 12-16 years categorized into two groups: 15 children with no detectable caries in Group I and 15 children with high caries (DMFS ≥10) in group II. MATERIALS AND METHODS: The stimulated salivary samples were inoculated in mitis salivarius bacitracin agar plates and growth of S. mutans was estimated. DNA extraction was done from whole blood and amplification was done with the help of real-time polymerase chain reaction technique. Oligonucleotide primers were designed to flank single nucleotide polymorphism in the gene. STATISTICAL ANALYSIS USED: The collected data was statistically analyzed by unpaired t-test, paired t-test, Chi-square test, Pearson correlation, and regression analysis. RESULTS: The difference in mean salivary S. mutans counts between the two groups was highly significant. Correlation between tuftelin gene polymorphism and dental caries susceptibility was not significant in both Group I and Group II. Only 4.1% of the variability in dental caries risk can be explained by interaction between tuftelin gene and S. mutans. CONCLUSIONS: Future research studies including parents and siblings should be carried out to focus on further investigation into the mechanism of this gene-environment interaction.

Human genes influence the interaction between Streptococcus mutans and host caries susceptibility: a genome-wide association study in children with primary dentition.

Streptococcus mutans is a well-known cause of dental caries, due to its acidogenicity, aciduricity, and ability to synthesize exopolysaccharides in dental plaques. Intriguingly, not all children who carry S. mutans manifest caries, even with similar characteristics in oral hygiene, diet, and other environmental factors. This phenomenon suggests that host susceptibility potentially plays a role in the development of dental caries; however, the association between host genetics, S. mutans, and dental caries remains unclear. Therefore, this study examined the influence of host gene-by-S. mutans interaction on dental caries. Genome-wide association analyses were conducted in 709 US children (<13 years old), using the dbGap database acquired from the center for oral health research in appalachia (COHRA) and the Iowa Head Start programmes (GEIRS). A generalized estimating equation was used to examine the gene-by-S. mutans interaction effects on the outcomes (decayed and missing/filled primary teeth due to caries). Sequentially, the COHRA and GEIRS data were used to identify potential interactions and replicate the findings. Three loci at the genes interleukin 32 (IL32), galactokinase 2 (GALK2), and CUGBP, Elav-like family member 4 (CELF4) were linked to S. mutans carriage, and there was a severity of caries at a suggestive significance level among COHRA children (P < 9 × 10-5), and at a nominal significance level among GEIRS children (P = 0.047-0.001). The genetic risk score that combined the three loci also significantly interacted with S. mutans (P < 0.000 1). Functional analyses indicated that the identified genes are involved in the host immune response, galactose carbohydrate metabolism, and food-rewarding system, which could potentially be used to identify children at high risk for caries and to develop personalized caries prevention strategies.

Novel caries loci in children and adults implicated by genome-wide analysis of families.

BACKGROUND: Dental caries is a common chronic disease among children and adults alike, posing a substantial health burden. Caries is affected by multiple genetic and environmental factors, and prior studies have found that a substantial proportion of caries susceptibility is genetically inherited. METHODS: To identify such genetic factors, we conducted a genome-wide linkage scan in 464 extended families with 2616 individuals from Iowa, Pennsylvania and West Virginia for three dental caries phenotypes: (1) PRIM: dichotomized as zero versus one or more affected primary teeth, (2) QTOT1: age-adjusted quantitative caries measure for both primary and permanent dentitions including pre-cavitated lesions, and (3) QTOT2: age-adjusted quantitative caries excluding pre-cavitated lesions. Genotyping was conducted for approximately 600,000 SNPs on an Illumina platform, pruned to 127,511 uncorrelated SNPs for the analyses reported here. RESULTS: Multipoint non-parametric linkage analyses generated peak LOD scores exceeding 2.0 for eight genomic regions, but no LOD scores above 3.0 were observed. The maximum LOD score for each of the three traits was 2.90 at 1q25.3 for PRIM, 2.38 at 6q25.3 for QTOT1, and 2.76 at 5q23.3 for QTOT2. Some overlap in linkage regions was observed among the phenotypes. Genes with a potential role in dental caries in the eight chromosomal regions include CACNA1E, LAMC2, ALMS1, STAMBP, GXYLT2, SLC12A2, MEGF10, TMEM181, ARID1B, and, as well as genes in several immune gene families. Our results are also concordant with previous findings from association analyses on chromosomes 11 and 19. CONCLUSIONS: These multipoint linkage results provide evidence in favor of novel chromosomal regions, while also supporting earlier association findings for these data. Understanding the genetic etiology of dental caries will allow designing personalized treatment plans based on an individual's genetic risk of disease.

Salivary protein polymorphisms and risk of dental caries: a systematic review.

Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions and proteins. Studies have described associations between salivary protein polymorphisms and dental caries experience, while others have shown no association with salivary proteins genetic variability. The aim of this study is to assess the influence of salivary protein polymorphisms on the risk of dental caries by means of a systematic review of the current literature. An electronic search was performed in PubMed, Scopus, and Virtual Health Library. The following search terms were used: "dental caries susceptibility," "dental caries," "polymorphism, genetics," "saliva," "proteins," and "peptides." Related MeSH headings and free terms were included. The inclusion criteria comprised clinical investigations of subjects with and without caries. After application of these eligibility criteria, the selected articles were qualified by assessing their methodological quality. Initially, 338 articles were identified from the electronic databases after exclusion of duplicates. Exclusion criteria eliminated 322 articles, and 16 remained for evaluation. Eleven articles found a consistent association between salivary protein polymorphisms and risk of dental caries, for proteins related to antimicrobial activity (beta defensin 1 and lysozyme-like protein), pH control (carbonic anhydrase VI), and bacterial colonization/adhesion (lactotransferrin, mucin, and proline-rich protein Db). This systematic review demonstrated an association between genetic polymorphisms and risk of dental caries for most of the salivary proteins.

Precision Dentistry in Early Childhood: The Central Role of Genomics.

Pediatric oral health is determined by the interaction of environmental factors and genetic influences. This is the case for early childhood caries, the most common disease of childhood. The complexity of exogenous-environmental factors interacting with innate biological predispositions results in a continuum of normal variation, as well as oral health and disease outcomes. Optimal oral health and care or precision dentistry warrants comprehensive understanding of these influences and tools enabling intervention on modifiable factors. This article reviews the current knowledge of the genomic basis of pediatric oral health and highlights known and postulated mechanistic pathways of action relevant to early childhood caries.

KLK4 Gene and Dental Decay: Replication in a South Brazilian Population.

OBJECTIVE: The objective of this research was to identify and replicate the participation of KLK4 gene polymorphisms in the susceptibility to dental decay. METHODS: A total of 200 patients were recruited using ICDAS criteria - 100 of them with dental caries and 100 with no history of the disease. Buccal cells were collected and the DNA was extracted and amplified using PCR. RESULTS: During the descriptive analysis, the variables ethnicity, biofilm, and gingivitis and the markers rs2242670 and rs2978642 were statistically significant. In the multivariate analysis, the marker rs2242670 and the variable biofilm maintained statistical significance. CONCLUSION: Genetic variations in the KLK4 gene may contribute to dental decay.

Genetic Polymorphisms in DEFB1 and miRNA202 Are Involved in Salivary Human ß-Defensin 1 Levels and Caries Experience in Children.

The antimicrobial peptides human ß-defensins (hBDs) are encoded by ß-defensin genes (DEFBs) and are possibly involved in caries susceptibility. In this study we aimed (1) to investigate the relationship between salivary hBDs and caries and (2) to evaluate the association of genetic polymorphisms in DEFB1 and microRNA202 (miRNA202) with salivary levels of hBDs and caries experience. Two data sets were available for this study, totalizing 678 Brazilian children. Dental examination and saliva collection were performed in all included children. The salivary level for hDB1, hBD2, and hBD4 was assessed by ELISA sandwich technique in 168 children. The DNA was extracted from saliva, and polymorphisms in DEFB1 and miRNA202 were analyzed by real-time PCR. Statistical analysis was performed to investigate the associations between caries experience, hBD salivary level, genotype, and allele distribution, with an alpha of 0.05. The hBD1 level was significantly higher in caries-free children (p < 0.0001). The miRNA202 was associated with a lower level of salivary hBD1 (p < 0.05). Also, the polymorphic distribution of miRNA202 was associated with caries (p = 0.006). The polymorphisms in DEFB1 were not associated with hBD salivary level and caries experience (p > 0.05). In conclusion, our results indicate that genetic polymorphism in miRNA202 is involved in hBD1 salivary level as well as caries experience in children.

Association of MBL2 Gene Polymorphism with Dental Caries in Saudi Children.

The high prevalence of dental caries in children worldwide is a major oral health problem which requires early intervention. Dental caries is mainly caused by the action of acids produced by bacteria in addition to many other factors. Recent genetic studies have reported that a number of genes are associated with the susceptibility to dental caries. The majority of these genes are associated with inflammation, increased susceptibility to infection, and dentine matrix formation. Using the TaqMan assay and direct DNA sequencing, the prevalence of 6 single-nucleotide polymorphisms (SNPs) in MMP9, MBL2, MMP2, and TIMP2 genes was determined in 102 children with caries and in 100 age-matched caries-free controls. Out of the 6 SNPs tested in the 4 selected genes, only rs11003125 in the MBL2 gene was shown to be associated with a high prevalence of caries in our cohort. In addition, haplotype analysis of the 6 SNPs tested revealed that certain haplotypes, namely GT of rs11003125G and rs7501477T and GT of rs7096206G and rs7501477T, were found to be associated with a high prevalence of dental caries in our cohort, while haplotype AG of rs17576A and rs7501477G was found to have a protective effect against dental caries. In conclusion, the data indicate that rs11003125 in the MBL2 gene was shown to be associated with a high prevalence of caries in our cohort, and 2 haplotypes are also involved in the increased susceptibility to dental caries.

Salivary protein polymorphisms and risk of dental caries: a systematic review

Abstract Dental caries is an oral pathology associated with both lifestyle and genetic factors. The caries process can be influenced by salivary composition, which includes ions and proteins. Studies have described associations between salivary protein polymorphisms and dental caries experience, while others have shown no association with salivary proteins genetic variability. The aim of this study is to assess the influence of salivary protein polymorphisms on the risk of dental caries by means of a systematic review of the current literature. An electronic search was performed in PubMed, Scopus, and Virtual Health Library. The following search terms were used: “dental caries susceptibility,” “dental caries,” “polymorphism, genetics,” “saliva,” “proteins,” and “peptides.” Related MeSH headings and free terms were included. The inclusion criteria comprised clinical investigations of subjects with and without caries. After application of these eligibility criteria, the selected articles were qualified by assessing their methodological quality. Initially, 338 articles were identified from the electronic databases after exclusion of duplicates. Exclusion criteria eliminated 322 articles, and 16 remained for evaluation. Eleven articles found a consistent association between salivary protein polymorphisms and risk of dental caries, for proteins related to antimicrobial activity (beta defensin 1 and lysozyme-like protein), pH control (carbonic anhydrase VI), and bacterial colonization/adhesion (lactotransferrin, mucin, and proline-rich protein Db). This systematic review demonstrated an association between genetic polymorphisms and risk of dental caries for most of the salivary proteins.

Caries and Innate Immunity: DEFB1 Gene Polymorphisms and Caries Susceptibility in Genetic Isolates from North-Eastern Italy.

BACKGROUND: The DEFB1 gene, encoding for the constitutively expressed human ß-defensin 1 (hBD1) antimicrobial peptide is a potential candidate when studying genetic susceptibility to caries. DEFB1 genetic variations have been reported as contributing to hBD1 production impairment, leading to a greater susceptibility to be infected by oral pathogens, also leading to periodontitis. METHODS: We analysed 5 DEFB1 polymorphisms, namely 3 functional single-nucleotide polymorphisms (SNPs) at the 5'-untranslated region (UTR), -52G>A (rs1799946), -44C>G (rs1800972), and -20G>A (rs11362), 2 SNPs at the 3'-UTR, c*5G>A (rs1047031) and c*87A>G (rs1800971) SNP located in potential miRNA binding sites, looking for possible correlations with the risk to develop caries in 654 adult subjects from isolated populations of north-eastern Italy. Dental caries prevalence was evaluated with the DMFT (decayed, missing, filled teeth) index, calculated after an accurate oral examination. DEFB1 SNP genotyping was performed with an Illumina 370k high-density SNP array. RESULTS: Two DEFB1 SNPs were significantly associated with the DMFT index: the strongest association emerged from rs11362 SNP (p = 0.008). In particular G/G homozygous individuals showed a higher DMFT index compared to both G/A heterozygous and A/A homozygous individuals; rs1799946 SNP was also significantly associated with DMFT (p = 0.030), and individuals homozygous for the T allele had a higher DMFT value compared to heterozygous C/T and homozygous C/C individuals. CONCLUSIONS: Our study replicated, on a larger number of individuals, previous findings showing the association between two 5'-UTR SNPs in the DEFB1 gene and DMFT, suggesting that these polymorphisms could be considered as potential markers for assessing the risk to develop caries.

Association study for the role of Matrix metalloproteinases 2 and 3 gene polymorphisms in dental caries susceptibility.

OBJECTIVE: Various exogenous and endogenous risk factors have been described as contributing to dental caries susceptibility. In the last decade it has been established that both pro and active forms of host derived Matrix metalloproteinases (MMPs) are present in the oral cavity. MMPs role in caries development has been hypothesized. The aim of this study was to analyse MMP2 (rs2287074) and MMP3 (rs679620) single nucleotide polymorphisms (SNPs) and their role in caries susceptibility. DESIGN: The two SNPs were analysed by PCR- restriction fragment length polymorphism (RFLP) in a sample of 102 ethnic Bulgarian volunteers (42 males and 60 females), all students in Sofia Medical University. RESULTS: Statistical analysis of the MMP2 SNP showed significant differences for the genotype frequencies between the caries free (CF, DMFT=0) and low caries experience (LCE, DMFT≤5) groups. Analysis for the non-synonymous MMP3 SNP found significant differences between both CF vs caries experience groups (LCE+ high caries experience (HCE, DMFT≥5)) and LCE vs HCE groups. The presence of allele G decreased the risk of HCE about 4 times. CONCLUSIONS: MMP2 and MMP3 genes are likely to be involved in caries susceptibility in our population. However, as dental caries is a multifactorial disorder and several genes are likely to have influence on it, it is reasonable to expect that SNPs, even those proven to be functional like rs679620, potentially play a significant, but not major role in the disease outcome.

Gene-environment Interactions in the Etiology of Dental Caries.

Dental caries is a multifactorial disease that can be conceptualized as an interaction between genetic and environmental risk factors. The aim of this study is to examine the effects of AMELX, CA6, DEFB1, and TAS2R38 gene polymorphism and gene-environment interactions on caries etiology and susceptibility in adults. Genomic DNA was extracted from the buccal mucosa, and adults aged 20 to 60 y were placed into 1 of 2 groups: low caries risk (DMFT ≤ 5; n = 77) and high caries risk (DMFT ≥ 14; n = 77). The frequency of AMELX (+522), CA6 (T55M), DEFB1 (G-20A), and TAS2R38 (A49P) single-nucleotide polymorphisms was genotyped with the polymerase chain reaction-restriction fragment length polymorphism method. Environmental risk factors examined in the study included plaque amount, toothbrushing frequency, dietary intake between meals, saliva secretion rate, saliva buffer capacity, mutans streptococci counts, and lactobacilli counts. There was no difference between the caries risk groups in relation to AMELX (+522) polymorphism (χ(2) test, P > 0.05). The distribution of CA6 genotype and allele frequencies in the low caries risk group did not differ from the high caries risk group (χ(2) test, P > 0.05). Polymorphism of DEFB1 (G-20A) was positively associated, and TAS2R38 (A49P) negatively associated, with caries risk (χ(2) test, P = 0.000). There were significant differences between caries susceptibility and each environmental risk factor, except for the saliva secretion rate (Mann-Whitney U test, P = 0.000). Based on stepwise multiple linear regression analyses, dental plaque amount, lactobacilli count, age, and saliva buffer capacity, as well as DEFB1 (G-20A), TAS2R38 (A49P), and CA6 (T55M) gene polymorphism, explained a total of 87.8% of the variations in DMFT scores. It can be concluded that variation in CA6 (T55M), DEFB1 (G-20A), and TAS2R38 (A49P) may be associated with caries experience in Turkish adults with a high level of dental plaque, lactobacilli count, and age and when saliva buffer capacity is low.