The Role of LTF, ENAM, and AMELX Gene Polymorphisms in Dental Caries Susceptibility: A Meta-Analysis

Association between ENAM polymorphisms and dental caries in children.

ObjectiveWith the development of human genomics, the genetic factors associated with dental caries have receiving increasing attention. This study was performed to evaluate the relationship between lactoferrin (LTF) and mannose-binding lectin 2 (MBL2) gene single nucleotide polymorphisms (SNPs) and dental caries susceptibility in Chinese children.MethodsThis prospective case–control study included 360 unrelated children (aged 12–15 years) who received oral health examinations and questionnaire surveys. The children were divided into two groups by counting the numbers of decayed, missing, and filled teeth (DMFT/dmft): case group (n = 162, DMFT/dmft ≥ 1) and control group (n = 198, DMFT/dmft = 0); non-invasive saliva samples were collected to extract genomic DNA. Six SNPs (rs2073495C/G, rs1042073C/T, rs10865941C/T, and rs1126477A/G in LTF; rs7096206C/G and rs7095891G/A in MBL2) were tested by mass spectrometry.ResultsThe study included 360 individuals with (85 boys and 77 girls) and without a history of caries (96 boys and 102 girls). There were no statistically significant differences in alleles and genotypes among the six SNPs between the two groups.ConclusionThere is no evidence that polymorphisms of LTF and MBL2 genes are associated with dental caries susceptibility in populations from northwest China; further confirmation is needed with larger sample sizes.

ObjectiveTo investigate the association between single nucleotide polymorphisms (SNPs) in six candidate genes (enamelin [ENAM]; tuftelin 1 [TUFT1]; matrix metallopeptidase 13 [MMP13]; interleukin 1 beta [IL1B]; interleukin 10 [IL10]; interleukin 1 receptor antagonist [IL1RN]) and dental caries in children from northwest China.MethodsThis case–control study enrolled children (12–15 years) who underwent routine dental examinations. The children were divided into two groups based on the presence of dental caries. A saliva sample was collected and seven SNPs (rs3806804A/G in ENAM, rs3811411T/G in TUFT1, rs2252070A/G and rs597315A/T in MMP13, rs1143627C/T in IL1B, rs1800872A/C in IL10 and rs956730G/A in IL1RN) were genotyped.ResultsA total of 357 children were enrolled in the study: 161 with dental caries and 196 without dental caries. No significant difference was found in the alleles and genotypes of five genes (ENAM, TUFT1, MMP13, IL10 and IL1RN) between those with and without dental caries. A significant relationship was found between the IL1B rs1143627C/T polymorphism and dental caries susceptibility with those carrying the rs1143627CT genotype having a lower risk of dental caries compared with those carrying the CC genotype (odds ratio 0.557; 95% confidence interval 0.326, 0.952).ConclusionThe IL1B rs1143627C/T polymorphism may be associated with dental caries susceptibility in children from northwest China.

Objective Lactoferrin (LTF) is a salivary glycoprotein involved in the innate immune defense of the oral cavity. Polymorphisms in the LTF gene have been implicated in oral and systemic diseases, but limited data are available regarding their association with dental caries. This study aimed to evaluate the relationship between LTF A/G polymorphism and caries susceptibility in Saudi children. Methods This case-control study included 40 children aged 4-12 years treated at the pediatric dental clinics at King Abdulaziz University (KAU), Jeddah, Saudi Arabia. Participants were divided into two groups: caries-free (Decayed, Missing, and Filled Teeth (DMFT) = 0, n = 20) and caries-experienced (DMFT ≥ 1, n = 20). Salivary DNA was extracted and genotyped using polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis.Descriptive statistics were used to summarize demographic and clinical characteristics, while associations between LTF genotypes and caries status were evaluated using the chi-square test. Results A statistically significant association was found between the LTF genotype and dental caries status (χ² = 10.09, p = 0.006). The heterozygous AG genotype was more frequent among children with caries, while the homozygous AA genotype was more prevalent among caries-free participants. Children with the AA genotype had significantly lower odds of having caries compared to those with the AG genotype (odds ratio (OR) = 0.073, 95% confidence interval (CI): 0.012-0.431). Conclusion The LTF A/G polymorphism is associated with caries susceptibility in Saudi children. These findings support a potential role for salivary genetic markers in early caries risk assessment, although larger studies are needed for validation.

Association of polymorphisms in genes involved in enamel formation, taste preference and immune response with early childhood caries in Saudi pre-school children.

ObjectiveThe aim of this study was to assess the role of ENAM rs3796703, LTF rs1126478, and TNF-α rs1800629 in high caries susceptibility. DesignThe present case–control study included 1005 unrelated children under 4 years old: 505 with severe caries (dmft index ≥4) and 500 who were caries-free (dmft index=0 and without white-spot lesions). Questionnaires were obtained from parents and gardians about the children’s diet and oral behavioural habits. All the children received dental examinations and oral swabbing for human genomic DNA collection. ENAM rs3796703, LTF rs1126478, and TNF-α rs1800629 were genotyped by Sanger sequencing. ResultsThe frequency of the ENAM rs3796703T allele (6.7% in the caries group and 4.2% in the caries-free group), CT genotype (12.7% in the caries group and 8.4% in the caries-free group), TNF-α rs1800629 A allele (4.8% in the caries group and 6.8% in the caries-free group), and AG genotype (8.7% in the caries group and 13.2% in the caries-free group) were significantly different between the caries and caries-free groups (p<0.05). No significant difference was found in the LTF rs1126478 allele frequency and genotype distribution between the two groups. The ENAM rs3796703 CT genotype increased caries susceptibility by 60.9% compared to the CC genotype (β=0.746, OR=1.609), and the TNF-α rs1800629 AG genotype reduced caries susceptibility by 47.4% compared to the GG genotype (β=−0.642, OR=0.526). In terms of habits covariates, prolongation of night feeding time by 1 month increased caries susceptibility by 3.3% (β=0.033, OR=1.033); additionally, sweets and acidic drinks consumption 1–2 times per day increased caries susceptibility by 218.2% (β=1.158, OR=3.182), and consumption 3 or more times pe/r day increased susceptibility by 883.5% (β=2.286, OR=9.835) compared to non-consumption. Topical fluoride application decreased caries susceptibility by 43.0% (β=−0.562, OR=0.570). ConclusionsThe ENAM and TNF-α genes are likely associated with caries experience in Chinese children. The ENAM rs3796703 CT genotype might be involved in caries susceptibility, while TNF-α rs1800629 AG genotype might be involved in caries protection.

Background:Dental caries is as primeval as humanity, but still, investigations are undergoing regarding the etiopathogenesis behind this multifactorial disease. Genetics is known to play a vital role in the etiology behind dental caries in addition to environmental and socioeconomic factors. Genetic variations like single-nucleotide polymorphisms (SNPs) were extensively studied in the past decade to portray the etiopathogenesis contributing to dental caries.Aim:This investigation was undertaken to analyze the ENAM gene SNP rs3796704 with caries susceptibility in ethnic young adult Tamil population of India.Materials and Methods:Out of 370 patients included, 215 patients belonged to the high caries group (Decayed, Missing and Filled Tooth [DMFT] ≥2) and 155 patients belonged to the low caries group (DMFT ≤ 1). DNA was extracted from the blood of all the individuals. SNP genotyping was performed utilizing tetra-primer amplification refractory mutation system–polymerase chain reaction with specific primers.Results:The genotyping results showed that there were no differences in allelic (P = 0.114) and genotypic frequencies (P = 0.159) between the high caries and low caries groups.Conclusion:Future studies can be conducted in larger samples and different ethnicities around the globe to analyze the role played by SNPs of enamel formation genes in cariogenesis.

The association between MMP13 rs2252070 polymorphism and caries susceptibility: A systematic review and meta-analysis

Dental caries can be conceptualized as an interaction between genetic and environmental factors. 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. 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. 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. The collected data was statistically analyzed by unpaired t-test, paired t-test, Chi-square test, Pearson correlation, and regression analysis. 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. Future research studies including parents and siblings should be carried out to focus on further investigation into the mechanism of this gene-environment interaction.

The association of genetic variants VDR Taq I rs731236 and AMLEX rs946252 with dental caries susceptibility and severity in Egyptian children.

To comprehensively investigate the effects of 25 variants in 15 genes on dental caries susceptibility in a cohort of Chinese children. 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). The association analysis revealed that rs11362 of defensin β1 (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. Out of 25 selected variants, only 2 of DEFB1 gene (rs11362 and rs1799946) were significantly associated with dental caries susceptibility in children.

Dental decay is a disease that is greatly affected by environmental components, but recently there have been an increasing number of documents supporting a genetic factor in the development of caries. The purpose of this study was to examine the association between dental caries and single-nucleotide polymorphisms in the AMELX gene. This research was carried out on 360 individuals of both sexes, who were referred to the dental school at the Shiraz University of Medical Sciences. In this research, individuals aged 20–65 years were divided into two groups: controls (decayed, missed, or filled teeth (DMFT) ≤ 5; n = 180) and cases (DMFT ≥ 14; n = 180). The tetra-primer ARMS-PCR technique was performed for genotyping the DNA extracted from blood cells. Analysis of the AMELX rs946252 polymorphism showed that the T allele of rs946252 was a significant protective factor against dental caries in Iranian adults (T vs. C: OR = 0.70, 95% CI: 0.49–0.98, P = 0.04). We demonstrated the significant differences in the genotype frequencies under two genetic models: overdominant (TC vs. TT + CC: OR 0.35, 95% CI 0.19–0.64, P = 0.0006) and recessive (CC vs. TC + TT: OR 2.57, 95% CI 1.39–4.76, P = 0.002). Our results show that the SNPs of the AMELX gene may be related with susceptibility to dental caries in Iranian adults.

In this study, to clarify the effects on dental caries susceptibility of mouse chromosome 2 in vivo, we used chromosome 2 substitution mice (termed consomic mice), B6-Chr2C3H. The consomic mice used in this study were based on high dental caries susceptibility strain C57BL/6CrSlc (B6), and only chromosome 2 from the low dental caries susceptibility strain C3H/HeSlc (C3H) was substituted. We induced dental caries in three inbred mice strains : B6, C3H and B6-Chr2C3H. All mice were weaned at 21 days, were fed on Diet#2000, and were infected with Streptococcus mutans JC-2 to induce dental caries. The mandible bones were extracted at 49 days and observed by microscope and Micro-focus X-ray computed tomography images. The caries status was evaluated by calculating the dental caries score using the modified Keyes method. Mean dental caries scores of B6-Chr2C3H, B6 and C3H were 8.1±3.4 (mean±S.D.), 46.5±1.3 and 2.2±1.0, respectively. Statistical analysis revealed that the dental caries score of B6-Chr2C3H was significantly low compared with the score of B6 and there was no difference in dental caries score between C3H and B6-Chr2C3H. The first fissures of the first molar in B6 and B6-Chr2C3H were similar having a slight fossa at center area and which were differ from that of C3H. However, there was no significant difference in dental caries score at the fissure among B6-Chr2C3H, B6 and C3H. And, the amount of saliva of B6-Chr2C3H was significantly low than C3H, and significantly high than B6. These results suggested that the major genetic factor responsible for dental caries susceptibility is located on mouse chromosome 2.

Objective To explore the correlation of caries susceptibility of patients with the immediate tooth polish, application of fluoride, and the patients' oral hygiene habits after interproximal enamel reduction (IER) in clinical practice. Methods The present study retrospectively collected 45 cases of IER (18 males and 27 females) in 196 tooth sites. Each sample was examined clinically and radiologically to obtain the incidence of caries, and the outcome was correlated with amount of IER, tooth polish, application of fluoride, and the brushing method and frequency for statistical analysis. Results The present study showed that there was no statistical significance among the amount of IER, the site of IER, the patients' brushing method, and the gender with the susceptibility of caries. However, there was statistical significance among the application of fluoride, tooth polish and brushing frequency with the susceptibility of caries. Conclusions The current research suggests that it is desirable to polish tooth and apply fluoride for patients with IER in clinical practices. In the meanwhile, the clinician should pay attention to patients' oral hygiene habits, especially brushing frequency, due to the positive correlation between the brushing frequency and incidence of caries. Key words: Interproximal enamel reduction; Fluoride; Tooth polish; Susceptibility of caries; Tooth brushing

Introduction The variety of the genetic factors playing role in development of dental caries calls for further research in this regard. The aim of the present study was to investigate the differences between caries-free adults and adults with dental caries in terms of polymorphism of caries-related genes (AMELX and ENAM). Methods The present case-control study was performed on 81 adults aged 18–24 years, 41 caries free, and 40 with a DMFT ≥ 4. A questionnaire containing background and demographic information (such as age, gender, time and type of latest dental check-ups, parent's education, oral self-care, and the place of residence in the first 12 years of life) was completed by participants at the time of examination. The blood sample was taken from each participant in the EDTA tube, and PCR was performed. Gene diversity of AMELX and ENAM genes was compared between the two groups. Results Regarding AMELX gene, in the caries-free group 33 (80.5%) and in the group with DMFT ≥ 4, 33 (82.5%) students had TT genotype, but this difference was insignificant. For ENAM gene, in the caries-free group 34 (82.9%) and in the group with DMFT ≥ 4, 39 (97.5%) students had TT genotype, but this difference was insignificant (P value = 0.048, CI 95%:0.02–1.27, and OR = 0.145). Conclusion There was no relationship between TT and TC genotypes of single nucleotide polymorphism of AMELX and ENAM gene and susceptibility to dental caries, but with increasing sample size, there may be a relationship between SNP of ENAM gene and being caries free.