A Polygenic Score Predicts Caries Experience in Elderly Swedish Adults.

Caries is a partially heritable disease, raising the possibility that a polygenic score (PS, a summary of an individual's genetic propensity for disease) might be a useful tool for risk assessment. To date, PS for some diseases have shown clinical utility, although no PS for caries has been evaluated. The objective of the study was to test whether a PS for caries is associated with disease experience or increment in a cohort of Swedish adults. A genome-wide PS for caries was trained using the results of a published genome-wide association meta-analysis and constructed in an independent cohort of 15,460 Swedish adults. Electronic dental records from the Swedish Quality Registry for Caries and Periodontitis (SKaPa) were used to compute the decayed, missing, and filled tooth surfaces (DMFS) index and the number of remaining teeth. The performance of the PS was evaluated by testing the association between the PS and DMFS at a single dental examination, as well as between the PS and the rate of change in DMFS. Participants in the highest and lowest deciles of PS had a mean DMFS of 63.5 and 46.3, respectively. A regression analysis confirmed this association where a 1 standard deviation increase in PS was associated with approximately 4-unit higher DMFS (P < 2 × 10-16). Participants with the highest decile of PS also had greater change in DMFS during follow-up. Results were robust to sensitivity analysis, which adjusted for age, age squared, sex, and the first 20 genetic principal components. Mediation analysis suggested that tooth loss was a strong mediating factor in the association between PS and DMFS but also supported a direct genetic effect on caries. In this cohort, there are clinically meaningful differences in DMFS between participants with high and low PS for caries. The results highlight the potential role of genomic data in improving caries risk assessment.

Assessing the association between tea intake and risk of dental caries and periodontitis: a two-sample Mendelian randomization study.

Tea is an indispensable beverage in people's daily life. However, the relationship between tea intake and dental caries and periodontitis is controversial. We extracted datasets for tea intake and oral diseases from genome-wide association studies (GWASs) conducted by the UK Biobank and the Gene Lifestyle Interactions in Dental Endpoints consortium. We selected 38 single-nucleotide polymorphisms (SNPs) significantly associated with tea intake as instrumental variables (IVs) (P < 5.0 × 10-8). Mendelian randomization (MR) was performed to investigate the potential causality between tea intake and caries and periodontitis. Multivariable Mendelian randomization (MVMR) analyses were utilized to estimate causal effects of tea intake on risk of caries and periodontitis after adjusting for smoking, body mass index (BMI), and socioeconomic factors. The results showed that higher tea intake was suggestively associated with fewer natural teeth (ß = - 0.203; 95% CI = 0.680 to 0.980; P = 0.029) and higher risk of periodontitis (OR = 1.622; 95% CI = 1.194 to 2.205; P = 0.002). After Bonferroni correction, the causality of tea intake on periodontitis remained significant. The significance of periodontitis disappeared after adjusting for the socioeconomic factors in MVMR (OR = 1.603; 95% CI = 0.964 to 2.666; P = 0.069). Tea intake had no association with risk of caries. Statistical insignificance of the heterogeneity test and pleiotropy test supported the validity of the MR study. Our results provide insight into the potential relationship between tea intake and oral diseases from a dietary lifestyle perspective, which may help prevent oral diseases.

AMELX gene association to early childhood caries in south-Indian children: a case-control study.

PURPOSE: Genetic variants of AMELX gene can affect the protein content, organization of enamel prisms, microstructure and microhardness of the enamel, thus altering the caries susceptibility. The present study aims to assess the association between polymorphisms rs17878486, rs5934997, and rs5933871 of AMELX gene and Early Childhood Caries (ECC). MATERIALS AND METHODS: This case-control study was conducted on 200 participants, aged 3-6 years, with 100 controls and 100 children with ECC. A questionnaire was used to collect demographic data, birth-weight, type of delivery, oral hygiene practices, feeding history and 24-h diet diary. DNA was isolated from blood and subjected to PCR followed by Sanger sequencing. RESULTS: The CC genotype of rs17878486 showed an OR of 1.93 (0.34-10.81; P = 0.73). In a recessive model, the CC genotype of rs17878486 reported an OR of 2.04 (0.36-11.40; P = 0.68); rs5593871 reported an OR of 1.00 (0.31-3.21). Statistically significant differences (P ≤ 0.05) between genotype and allele frequencies of rs17878486, rs5934997, and rs5933871 were not observed between children with ECC and the controls. CONCLUSION: Polymorphisms of AMELX gene did not show a significant association with ECC in this population. However, documentation of genetic data in a global context of ECC may be essential for the future.

Sjögren's Disease and Oral Health: A Genetic Instrumental Variable Analysis.

Epidemiological studies have consistently shown that Sjögren's disease (SjD) increases the risk of dental caries. Despite similar evidence indicating an elevated risk of periodontitis, SjD remains a disputed risk factor for this disease. The risk of bias in observational research is a major impediment to confirming this link. Within an instrumental variable framework, genetic variants associated with a risk factor can be used to proxy its effect on an outcome while avoiding common sources of observational study bias. In this study, we leveraged an instrumental variable approach to investigate whether SjD affects the risk of caries and periodontitis. A total of 57 genetic variants strongly associated with SjD were identified from a genome-wide association study of 2,247 European descent cases and 332,115 controls. We tested for associations of these genetic instruments with caries (measured as the number of decayed, missing, and filled surfaces in 26,792 individuals) and periodontitis (17,353 clinical periodontitis cases and 28,210 European controls). Several sensitivity analyses were used to further validate the primary inverse variance weighted (IVW) estimate. IVW analysis revealed an adverse effect of SjD on caries (ß = 0.039, P = 6.3e-16) and periodontitis (odds ratio = 1.033, P = 2.3e-05). Sensitivity analyses, conducted to assess the robustness to potential violations of instrumental variable assumptions, further support these findings. Our results showed that SjD has a detrimental effect on caries and also suggest that SjD promotes periodontitis.

Dental pain report in children and genetic polymorphism (rs4818) in Catechol-O-Methyltransferase (COMT) gene: a cross- sectional study.

AIM: Polymorphisms in the COMT gene can alter enzymatic functions, raising levels of endogenous catecholamines, which stimulates beta-adrenergic receptors related to pain. This study aimed to evaluate whether a polymorphism in the COMT gene (rs4818) is associated with dental pain in children. METHODOLOGY: A cross-sectional study was conducted with a representative sample of 731 pairs of children and parents randomly selected from a population-based sample of eight-year-old children. Reports of dental pain was evaluated using a question directed at the parents and self-reported pain using the Faces Pain Scale - Revised. Dental caries experience was determined using the Decayed, Missing, and Filled Teeth (DMFT) index. For genetic analysis, DNA was obtained from oral mucosa epithelial cells of 352 children randomly selected from the initial sample. RESULTS: Children with the CC genotype had higher odds of reporting moderate to intense pain than those with the GG genotype (OR=3.60; 95% CI=0.80-16.20; p=0.03). These same children had greater odds of parental reports of pain (OR=1.93; 95% CI=0.91-4.08; p=0.02). Moreover, lower schooling of parents/guardians and caries experience in the primary dentition were significantly associated with greater odds of a parental report of dental pain (OR=2.06; 95% CI=1.47-2.91; p<0.001; OR=6.26; 95% CI=4.46-8.78; p<0.001). CONCLUSIONS: The rs4818 polymorphism of the COMT gene is associated with dental pain. Children with the C allele are more likely to report higher levels of pain. Clinical Relevance: Even though the experience of pain is subjective and multifactorial, this study raises the hypothesis that there is a genetic predisposition to dental pain that should be considered in clinical practice.

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.

Oral microbiota analyses of paediatric Saudi population reveals signatures of dental caries.

BACKGROUND: Oral microbiome sequencing has revealed key links between microbiome dysfunction and dental caries. However, these efforts have largely focused on Western populations, with few studies on the Middle Eastern communities. The current study aimed to identify the composition and abundance of the oral microbiota in saliva samples of children with different caries levels using machine learning approaches. METHODS: Oral microbiota composition and abundance were identified in 250 Saudi participants with high dental caries and 150 with low dental caries using 16 S rRNA sequencing on a NextSeq 2000 SP flow cell (Illumina, CA) using 250 bp paired-end reads, and attempted to build a classifier using random forest models to assist in the early detection of caries. RESULTS: The ADONIS test results indicate that there was no significant association between sex and Bray-Curtis dissimilarity (p ~ 0.93), but there was a significant association with dental caries status (p ~ 0.001). Using an alpha level of 0.05, five differentially abundant operational taxonomic units (OTUs) were identified between males and females as the main effect along with four differentially abundant OTUs between high and low dental caries. The mean metrics for the optimal hyperparameter combination using the model with only differentially abundant OTUs were: Accuracy (0.701); Matthew's correlation coefficient (0.0509); AUC (0.517) and F1 score (0.821) while the mean metrics for random forest model using all OTUs were:0.675; 0.054; 0.611 and 0.796 respectively. CONCLUSION: The assessment of oral microbiota samples in a representative Saudi Arabian population for high and low metrics of dental caries yields signatures of abundances and diversity.

Hub genes and pathways related to caries-free dental biofilm: clinical metatranscriptomic study.

OBJECTIVE: This study aimed to evaluate the microbial functional profile of biofilms related to caries-free (CF, n = 6) and caries-arrested (CI, n = 3) compared to caries-active (CA, n = 5) individuals. MATERIALS AND METHODS: A metatranscriptomic was performed in supragingival biofilm from different clinical conditions related to caries or health. Total RNA was extracted and cDNAs were obtained and sequenced (Illumina HiSeq3000). Trimmed data (SortMeRNA) were submitted to the SqueezeMeta pipeline in the co-assembly mode for functional analysis and further differential gene expression analysis (DESeq2) and weighted gene co-expression network analysis (WCGNA) to explore and identify gene modules related to these clinical conditions. RESULTS: A total of 5303 genes were found in the metatranscriptomic analysis. A co-expression network identified the most relevant modules strongly related to specific caries status. Correlation coefficients were calculated between the eigengene modules and the clinical conditions (CA, CI, and CF) discriminating multiple modules. CA and CI showed weak correlation coefficient strength across the modules, while the CF condition presented a very strong positive correlation coefficient (r = 0.9, p value = 4 × 10-9). Pearson's test was applied to further analyze the module membership and gene significance in CF conditions, and the most relevant were HSPA1s-K03283, Epr- K13277, and SLC1A-K05613. Gene Ontology (GO) shows important bioprocesses, such as two-component system, fructose and mannose metabolism, pentose and glucuronate interconversions, and flagellar assembly (p-adjust < 0.05). The ability to use different carbohydrates, integrate multiple signals, swarm, and bacteriocin production are significant metabolic advantages in the oral environment related to CF. CONCLUSIONS: A distinct functional health profile could be found in CF, where co-occurring genes can act in different pathways at the same time. Genes HSPA1s, Epr, and SLC1A may be appointed as potential biomarkers for caries-free biofilms. CLINICAL RELEVANCE: Potential biomarkers for caries-free biofilms could contribute to the knowledge of caries prevention and control.

The contribution of genetics to dental caries, oral habits and occlusal traits in Turkish twins: A comparative study.

OBJECTIVE: The aims of this study were to investigate and compare the prevalence of dental caries and the frequency of oral habits, molar relationships and occlusal traits between children of multiple births, and singletons, and to determine the relative contributions of genetics and environmental factors to these parameters by using twin study design. METHODS: The study group consisted of 345 multiple births (34 monozygotic and 122 dizygotic twin pairs, 11 sets of triplets) and 345 singletons between the ages of 2 and 17. The prevalence of dental caries, and the frequency of tooth brushing, the children's oral habits, molar relationships, and occlusal traits were recorded. RESULTS: The percentage of children who brushed their teeth more than twice daily was statistically significantly higher in multiple births than in singletons. Higher correlation coefficients were found in dental caries index, except for decayed, filled (df) (2-5 age group) and filled (f) (6-11 age group), in the monozygotic twin pairs compared to those in the dizygotic twin pairs. In children between the ages of 6 and 11 years, mouth breathing, bruxism, lip biting, and pencil biting were higher in singletons than in children of multiple births. There were statistically significant differences between children of multiple births and singletons, with increased overjet in the 2-5 year age group being observed. CONCLUSION: When analyzing these parameters, environmental factors must also be investigated. Due to the low incidence of twin births, longitudinal follow-up studies with more twin pairs are necessary to determine whether these results are generalizable.

Genome-wide association study identifies novel caries-associated loci showing sex-specificity-A study on the Northern Finland Birth Cohort 1966.

A genome-wide association study was performed in sex-stratified groups representing three different caries phenotypes among adults. The study sample consisted of 46-year-old participants of the Northern Finland Birth Cohort 1966 study (n = 1481). The phenotypes for analyses were the dentin caries phenotype (persons having at least one tooth with dentin caries lesion), and the enamel caries phenotype (those having teeth with more than 10 enamel caries lesions), while the control group had <10 enamel caries lesions and no teeth with dentin caries, respectively. A third phenotype dubbed the caries severity phenotype had a below-average number of teeth with initial lesions and at least one extensive dentin caries lesion; their controls had an above-average number of teeth with initial caries lesions and no teeth with extensive dentin caries lesions. All analyses were performed for the whole group and for sex-stratified subgroups. In females, loci in chromosomes 2, 5, and 15 showed a statistically significant association with caries severity. In males, there was a novel association between chromosome 5 and dentin caries. The results of this study may suggest a genetic background of caries among adults. In the future, the detection of genetic predisposing variants may allow the identification of patients at risk for caries, even in the absence of behavioral and environmental risk factors.

[Polymorphisms associated with dental caries in pediatric populations: a systematic review]. / Polimorfismos asociados a la caries dental en poblaciones pediátricas: una revisión sistemática.

Single nucleotide polymorphisms (SNPs) have been reported to play an important role in the etiology of dental caries. The aim of this research was, through a systematic review, to identify SNPs recently associated with dental caries in pediatric populations. We included studies performed in humans up to 18 years of age that evaluated the relationship between SNPs and dental caries from 2017 to 2022. Articles that covered other study variables were excluded. PubMed, ScienceDirect and Web of Science were used to search for information and the included articles were evaluated with one of the Joanna Briggs Institute's tools. Twenty-five articles were selected, 60% of which were given high methodological quality. A total of 10,743 research subjects, ranging in age from 20 months to 17 years, participated in the study. The SNPs considered risk factors were identified in the genes miRNA202, VDR, AMELX, TUFT1, KLK4, MBL2, ENAM, DEFB1, HLA-DRB1, TAS1R1, DSPP, RUNX2 and MMP13; those considered protective factors were identified in the genes MMP20, AMBN, MMP9, TIMP2, TNF-α, VDR, IL1B, ENAM and HLA-DRB1. This systematic review presents the genetic polymorphisms that are associated with the etiology of caries in children and adolescents, some of which act as risk factors and others as protective factors against the disease.

Se ha reportado que los polimorfismos de nucleótido único (SNPs) juegan un papel importante en la etiología de la caries dental. El objetivo de esta investigación fue, a través de una revisión sistemática, identificar los SNPs asociados recientemente a la caries dental en poblaciones pediátricas. Se incluyeron estudios realizados en humanos de hasta 18 años de edad que evaluaron la relación entre los SNPs y la caries dental, publicados desde el 2017 hasta el 2022. Se excluyeron los artículos que abarcaron otras variables de estudio. PubMed, ScienceDirect y Web of Science se utilizaron para la búsqueda de información y los artículos incluidos fueron evaluados con una de las herramientas del Instituto Joanna Briggs. Fueron seleccionados 25 artículos, al 60% de ellos se le otorgó calidad metodológica alta. En total participaron 10,743 sujetos de invetigación, cuyas edades variaron de 20 meses a 17 años. Los SNPs considerados factores de riesgo fueron identificados en los genes miRNA202, VDR, AMELX, TUFT1, KLK4, MBL2, ENAM, DEFB1, HLA-DRB1, TAS1R1, DSPP, RUNX2 y MMP13, los considerados factores de protección se identificaron en los genes MMP20, AMBN, MMP9, TIMP2, TNF-α, VDR, IL1B, ENAM y HLA-DRB1. Esta revisión sistemática expone los polimorfismos genéticos que se encuentran asociados a la etiología de la caries en niños y adolescentes, algunos de los cuales actúan como factores de riesgo y otros como factores de protección ante la enfermedad.

Association of MTR and MTRR genes and oral health-related quality of life in children with dental caries.

This study aimed to assess whether genetic polymorphisms in MTR and MTRR are potential biomarkers of oral health-related quality of life (OHRQoL) in children with caries. A cross-sectional study was designed wherein pairs of parents/caregivers and children (aged two-five years) were selected. Clinical examination was used to detect dental caries, which were classified as low-severity and high-severity caries. The Early Childhood Oral Health Impact Scale (ECOHIS) questionnaire was used to assess OHRQoL. Genomic DNA extracted from the saliva was used to analyze two missense genetic polymorphisms: MTR (rs1805087) and MTRR (rs1801394). Mann-Whitney non-parametric test was used to analyze candidate genes with OHRQoL scale and domain, with a significance level of p≤0.05. MTR (rs1805087) was found associated (p = 0.05) with children's OHRQoL subscale scores in the dominant model (GG + AG). Genetic polymorphisms in MTR may increase the risk of poor OHRQoL in children with caries. Further studies are needed to investigate genetics, molecular factors, and OHRQoL.

Bacterial Community Modifies Host Genetics Effect on Early Childhood Caries.

By age 5, approximately one-fifth of children have early childhood caries (ECC). Both the oral microbiome and host genetics are thought to influence susceptibility. Whether the oral microbiome modifies genetic susceptibility to ECC has not been tested. We test whether the salivary bacteriome modifies the association of a polygenic score (PGS, a score derived from genomic data that summarizes genetic susceptibility to disease) for primary tooth decay on ECC in the Center for Oral Health Research in Appalachia 2 longitudinal birth cohort. Children were genotyped using the Illumina Multi-Ethnic Genotyping Array and underwent annual dental examinations. We constructed a PGS for primary tooth decay using weights from an independent, genome-wide association meta-analysis. Using Poisson regression, we tested for associations between the PGS (high versus low) and ECC incidence, adjusting for demographic characteristics (n = 783). An incidence-density sampled subset of the cohort (n = 138) had salivary bacteriome data at 24 mo of age. We tested for effect modification of the PGS on ECC case status by salivary bacterial community state type (CST). By 60 mo, 20.69% of children had ECC. High PGS was not associated with an increased rate of ECC (incidence rate ratio, 1.09; 95% confidence interval [CI], 0.83-1.42). However, having a cariogenic salivary bacterial CST at 24 mo was associated with ECC (odds ratio [OR], 7.48; 95% CI, 3.06-18.26), which was robust to PGS adjustment. An interaction existed between the salivary bacterial CST and the PGS on the multiplicative scale (P = 0.04). The PGS was associated with ECC (OR, 4.83; 95% CI, 1.29-18.17) only among individuals with a noncariogenic salivary bacterial CST (n = 70). Genetic causes of caries may be harder to detect when not accounting for cariogenic oral microbiomes. As certain salivary bacterial CSTs increased ECC risk across genetic risk strata, preventing colonization of cariogenic microbiomes would be universally beneficial.

Single nucleotide polymorphisms of enamel formation genes and early childhood caries - systematic review, gene-based, gene cluster and meta-analysis.

Introduction: Genetic polymorphisms of genes regulating amelogenesis can alter susceptibility to Early Childhood Caries (ECC). This systematic review aims to analyze associations between single-nucleotide polymorphisms of enamel formation genes and ECC. Methods: Search was conducted across PUBMED, CINAHL, LILACS, SCOPUS, EMBASE, Web of Science, Genome-Wide Association Studies databases from January 2003 to September 2022. This was supplemented by hand search. Totally 7124 articles were identified and 21 articles that satisfied the inclusion criteria proceeded to data extraction. Quality assessment was done using the Q-Genie tool. Results: Quantitative synthesis revealed that homozygous genotype AA of rs12640848 was significantly higher in children with ECC with an odds ratio of 2.36. Gene-based analysis revealed significant association between six variants of AMBN, four variants of KLK4, two variants of MMP20, and a single variant of each of MMP9 and MMP13 genes and ECC. The Bonferroni corrected-log10 P value of amelogenesis gene Cluster was 2.25 (0.05/88 = 5.6 × 10-4). Search Tool for Retrieval of Interacting Genes and Proteins plot constructed to comprehend the protein-protein interaction revealed the presence of four functional clusters. Gene function prediction using Multiple Association Network Integration Algorithm revealed that physical interaction between these genes was 69.3%. Conclusion: Polymorphisms of genes regulating amelogenesis can influence the susceptibility to ECC. AA genotype of rs12640848 may increase the susceptibility to ECC. Gene-based analysis revealed a significant association between multiple polymorphisms of genes regulating amelogenesis and ECC.

Association Between the SLC2A2 Gene rs1499821 Polymorphism and Caries Susceptibility.

Objectives: This study was designed to analyze the association between the SLC2A2 rs1499821 polymorphism and caries susceptibility in the Chinese Han, Zhuang, and Baikuyao populations. Materials and Methods: The present case-control study included 1067 12-year-old children: 481 with caries (142 Han, 166 Zhuang and 173 Baikuyao) and 586 who were caries-free (135 Han, 178 Zhuang and 273 Baikuyao). Questionnaires about diet and oral habits were obtained from all subjects. All of the children received dental examinations and DNA collection. The SLC2A2 rs1499821 SNP was genotyped using the SNPscan technique. Results: The rs1499821 T polymorphism was significantly associated with caries susceptibility in both the Han population and the combined populations of the three ethnic subgroups. SLC2A2 rs1499821 was associated with caries susceptibility in the dominant model in the Han (p = 0.045) population and the combined (p = 0.038) group. The CT+TT genotypes at rs1499821 were associated with a higher risk of caries in the Han (OR = 1.69, adjusted 95% CI: 1.01-2.81) and combined (OR = 1.33, adjusted 95% CI: 1.02-1.74) populations. In both Han (p = 0.009) and the combined populations (p = 0.004), there were statistically significant associations between the frequency of sweet food intake and dental caries. However, the rs1499821 polymorphisms did not associate with the frequency of sweet food intake in these ethnic subgroups. Conclusion: In the Han population, the SLC2A2 rs1499821 T allele and the frequency of sweet food intake may be regarded as risk factors for caries susceptibility. The SLC2A2 rs1499821 T allele had no association with the frequency of sweet food intake in any of the three ethnic groups.

Association between Carbonic Anhydrase VI Gene Copy Number Variations and Dental Caries Experience.

The current study examined the association between the carbonic anhydrase VI (CA VI) copy number variations (CNVs) and dental caries experience in adults. In total, 202 of 35-72 years old subjects participating in the Lithuanian National Oral Health Survey (LNOHS) agreed to provide saliva samples; thus, their data were included in the current study. Information about sociodemographic, environmental, and behavioural determinants was acquired via the self-administered World Health Organization (WHO) questionnaire. Fluoride levels in the drinking water were recorded based on information provided by water suppliers. Dental caries experience was recorded by one calibrated examiner using the WHO criteria for recording caries on smooth (including proximal, buccal, and oral) or occlusal surfaces. Caries experience was measured as the total number of decayed (D3), missing (M), filled (F) surfaces. DNA was extracted from saliva samples to examine CA VI CNVs using the QX200 Droplet Digital PCR system. Negative binomial regression and Poisson regression analyses were employed for data analyses. Based on multivariable regression analyses, higher copy number of CA VI were associated with higher caries experience on smooth surfaces (IRR 1.04, 95% CI: 1.005-1.08) and occlusal surfaces (IRR 1.02, 95% CI: 1.003-1.04). Positive associations between higher copy number of CA VI and higher caries experience on smooth and occlusal surfaces were found, suggesting that the CA VI coding gene may be associated with caries development. Future studies are needed to validate our results and to examine the underlying mechanisms of such associations.

Impact of tooth mineral tissues genes on dental caries: A birth-cohort study.

OBJECTIVE: We aimed to investigate whether Single Nucleotide Polymorphisms present in the genes of tooth mineral tissues influence dental caries trajectory across the life course, and if there is an epistatic (gene-gene) interaction between these SNPs. METHODS: A representative sample of all 5,914 births from the 1982 Pelotas birth cohort study was prospectively investigated. Dental caries trajectory across the life course was assessed at 15(n = 888), 24(n = 720), and 31 years old(n = 539). Group-based trajectory modeling was used to identify distinct subgroups of individuals whose caries measurements followed a similar pattern over time. Genetic material was collected, and individuals were genotyped [rs4970957(TUFT1), rs1711437(MMP20), rs1784418(MMP20), rs2252070(MMP13), rs243847(MMP2), rs2303466(DLX3), rs11656951(DLX3), rs7501477(TIMP2), rs388286(BMP7), and rs5997096(TFIP11)]. Analyzes were performed for allele and genotype using logistic regression and generalized multifactor dimensionality reduction for epistatic interactions. RESULTS: The analyses included 678 individuals, those with allele C (OR=0.74, CI95%[0.59-0.92]), genotype CC in the additive effect (OR=0.52, CI95%[0.31-0.89]), and the genotype TC/CC in dominant effect (OR=0.72, CI95%[0.53-0.98]) on the rs243847(MMP2) were associated with low caries trajectory. Individuals with the allele T (OR=0.79, CI95%[0.64-0.98]) and the genotype TC/CC in dominant effect (OR=0.66, CI95%[0.47-0.95]) on the rs5997096(TFIP11) were associated with low caries trajectory. Positive epistatic interactions were observed involving two (MMP2 and BMP7; p = 0.006) and three (TUFT1, MMP2, and TFIP11; p<0.001) loci and high caries trajectory. CONCLUSIONS: Some SNPs present in the genes of tooth mineral tissues were associated with caries trajectory and epistatic interactions increasing the network of SNPs involved in individual caries experience. CLINICAL SIGNIFICANCE: Single nucleotide polymorphisms in the pathway of tooth mineral tissues genes may contribute significantly to the individual caries experience across the life course.

Development of the oral resistome during the first decade of life.

Antibiotic overuse has promoted the spread of antimicrobial resistance (AMR) with significant health and economic consequences. Genome sequencing reveals the widespread presence of antimicrobial resistance genes (ARGs) in diverse microbial environments. Hence, surveillance of resistance reservoirs, like the rarely explored oral microbiome, is necessary to combat AMR. Here, we characterise the development of the paediatric oral resistome and investigate its role in dental caries in 221 twin children (124 females and 97 males) sampled at three time points over the first decade of life. From 530 oral metagenomes, we identify 309 ARGs, which significantly cluster by age, with host genetic effects detected from infancy onwards. Our results suggest potential mobilisation of ARGs increases with age as the AMR associated mobile genetic element, Tn916 transposase was co-located with more species and ARGs in older children. We find a depletion of ARGs and species in dental caries compared to health. This trend reverses in restored teeth. Here we show the paediatric oral resistome is an inherent and dynamic component of the oral microbiome, with a potential role in transmission of AMR and dysbiosis.

Genome-Wide Analysis of Dental Caries Variability Reveals Genotype-by-Environment Interactions.

Genotype-by-environment interactions (GEI) may influence dental caries, although their effects are difficult to detect. Variance quantitative trait loci (vQTL) may serve as an indicator of underlying GEI effects. The aim of this study was to investigate GEI effects on dental caries by prioritizing variants from genome-wide vQTL analysis. First, we identified vQTLs from ~4.3 M genome-wide variants in three cohorts of white children aged 3-5 (n = 396, n = 328, n = 773) using Levene's test. A total of 39 independent vQTLs with p < 1 × 10-6 were identified, some of which were located in or near genes with plausible biological roles in dental caries (IGFBP7, SLC5A8, and SHH involved in tooth development and enamel mineralization). Next, we used linear regression to test GEI effects on dental caries with the 39 prioritized variants and self-reported environmental factors (demographic, socioeconomic, behavioral, and dietary factors) in the three cohorts separately. We identified eight significant GEIs indicating that children with vQTL risk genotypes had higher caries experience if they had less educated parents, lower household/parental income, brushed their teeth less frequently, consumed sugar-sweetened beverages more frequently, were not breastfed, and were female. We reported the first genome-wide vQTL analysis of dental caries in children nominating several novel genes and GEI for further investigations.

Genes and single nucleotide polymorphisms in the pathway of saliva and dental caries: a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to investigate the influence of single nucleotide polymorphisms (SNPs), related to genes in salivary composition and flow, on dental caries experience. Sixteen studies were included in the systematic review and ten in the meta-analysis. Forty-four SNPS, covering four genes (CA6, AQP2, AQP5, and MUC5B) were identified. Most of the SNPs were not associated with caries in meta-analysis. Homozygous TT genotype of the SNP CA6 rs17032907(C/T) was associated with caries [OR = 3.23(1.39-7.49)]. The pool effect of the SNPs assessed in AQP5 was associated with a reduction in the likelihood of caries [OR = 0.75(0.59-0.95)]. Considering all SNPs of salivary composition and flow, the effect allele was associated with a 75% increase in the likelihood of caries [OR = 1.75(1.06-2.89)] in the homozygous genotype. The present findings showed that the genes in salivary composition and flow can play an important role in dental caries experience.