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1.
Biofouling ; 36(9): 1100-1116, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33327793

RESUMO

The aim of this systematic review and meta-analysis was to pool the data on Single Nucleotide Polymorphisms (SNPs) in immune response genes associated with dental caries. Nineteen studies were included in the review and 18 in the meta-analysis. Twenty-two SNPs were evaluated, which are linked to six different genes (MBL2, LFT, MASP2, DEFB1, FCN2 and MUC5B). Most SNPs (81.8%) are related to the possible functional impact on protein coding. The MBL2 gene was associated with caries experience in the analysis of the homozygote (OR = 2.12 CI95%[1.12-3.99]) and heterozygote (OR = 2.22 CI95%[1.44-3.44]) genotypes. The MUC5B gene was associated according to an analysis of the heterozygous genotype (OR = 1.83 CI95%[1.08-3.09]). Thus, SNPs related to immune response genes are linked to the phenotype of caries experience. Although the meta-analysis showed that the genes MBL2 and MUC5B were associated with caries, these results should be interpreted with caution due to the quality of the evidence.


Assuntos
Cárie Dentária , Cárie Dentária/genética , Suscetibilidade à Cárie Dentária , Genótipo , Humanos , Imunidade , Serina Proteases Associadas a Proteína de Ligação a Manose , Polimorfismo de Nucleotídeo Único , beta-Defensinas
2.
Braz Oral Res ; 34: e055, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578798

RESUMO

This study was performed to evaluate the interplay between dental caries, nutritional status, and genetic polymorphisms in TAS1R1 and TAS1R2 (taste receptor, type 1, member 1 and 2) in preschool children and pre-adolescents. We included 525 subjects (306 preschool children and 219 pre-adolescents). Parents/caregivers answered a self-administered questionnaire about their children's systemic health, characteristics, oral hygiene habits, and diet. Clinical examination was performed to evaluate dental caries and nutritional status. Saliva samples were collected for DNA extraction. The genotyping of rs17492553 ( TAS1R1 ), rs3935570, and rs4920566 ( TAS1R2 ) polymorphisms was performed using real-time PCR with Taqman Genotyping Master Mix and SNP assay. Both univariate and multivariate Poisson regression analyses with robust variance were used for the data analysis. In preschool children, consumption of sweets between meals increased the prevalence of dental caries by 85% (PR c = 1.85; 95%CI 1.39-2.46; p < 0.001), whereas in pre-adolescents, this prevalence increased by 34% (PR a = 1.34; 95%CI 1.11-1.62; p = 0.002), regardless of genetic polymorphisms . Moreover, individuals carrying at least one allele C in rs17492553 presented 23% more prevalence of dental caries (PR a = 1.23; 95%CI 1.02-1.49 p = 0.030). Nutritional status was not associated with dental caries, neither with genetic polymorphisms . Consumption of sweets between meals increased the prevalence of dental caries. In pre-adolescents, rs17492553 genetic polymorphism in TAS1R1 was associated with dental caries.


Assuntos
Cárie Dentária/genética , Estado Nutricional/genética , Polimorfismo Genético , Receptores Acoplados a Proteínas-G/genética , Adolescente , Brasil/epidemiologia , Criança , Índice CPO , Cárie Dentária/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Reação em Cadeia da Polimerase em Tempo Real , Análise de Regressão , Fatores de Risco , Inquéritos e Questionários , Paladar/genética
3.
BMC Med Genet ; 21(1): 114, 2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32460726

RESUMO

BACKGROUND: The pathogenesis of dental caries remains unclear, with increasing evidence suggesting that genetic susceptibility plays an essential role. Previous studies have reported the association between genetic polymorphisms in lactotransferrin (LTF) and the risk of dental caries with inconsistent results. METHODS: A systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases was performed by two authors independently for papers published before December 5, 2019 on the association between genetic variants in LTF and the risk of dental caries. We adopted the subsequent inclusion criteria to assess study eligibility: 1) The studies were based on human subjects; 2) the presence of dental caries should be screened for in both the case group and the control group; and 3) genotype data on variants in LTF were available in both the case group and the control group. We calculated odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) by using random-effects models to assess the association of genetic variants in LTF with the risk of dental caries. We also performed a gene-based analysis to explore the joint association of multiple genetic variants in LTF with the risk of dental caries. RESULTS: Our systematic literature search identified six relevant papers for analysis. We found no significant association between rs1126478 and the risk of dental caries when meta-analysing the genotype distribution between subjects with dental caries and those without dental caries (additive model: OR = 1.41; 95% CI = 0.98-2.02; P = 0.065). However, further analysis indicated that rs1126478 was associated with dental risk in subjects who had moderate or severe dental caries compared to those without dental caries (P < 0.0001). The gene-based analysis indicated that multiple genetic variants in LTF were jointly associated with the risk of dental caries (P = 0.002). CONCLUSIONS: The present meta-analysis revealed some evidence of the association between rs1126478 and dental caries and that multiple genetic variants in LTF are jointly associated with the risk of dental caries. Our findings need to be validated by larger studies that adjust for important confounding factors for the risk of dental caries.


Assuntos
Cárie Dentária/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Variação Genética , Lactoferrina/genética , Alelos , Biologia Computacional/métodos , Cárie Dentária/diagnóstico , Feminino , Humanos , Masculino , Modelos Genéticos , Razão de Chances , Viés de Publicação , Medição de Risco
4.
BMC Med Genet ; 21(1): 97, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32380970

RESUMO

BACKGROUND: Amelogenesis imperfecta (AI) is a highly heterogeneous group of hereditary developmental abnormalities which mainly affects the dental enamel during tooth development in terms of its thickness, structure, and composition. It appears both in syndromic as well as non-syndromic forms. In the affected individuals, the enamel is usually thin, soft, rough, brittle, pitted, chipped, and abraded, having reduced functional ability and aesthetics. It leads to severe complications in the patient, like early tooth loss, severe discomfort, pain, dental caries, chewing difficulties, and discoloration of teeth from yellow to yellowish-brown or creamy type. The study aimed to identify the disease-causing variant in a consanguineous family. METHODS: We recruited a consanguineous Pashtun family of Pakistani origin. Exome sequencing analysis was followed by Sanger sequencing to identify the pathogenic variant in this family. RESULTS: Clinical analysis revealed hypomaturation AI having generalized yellow-brown or creamy type of discoloration in affected members. We identified a novel nonsense sequence variant c.1192C > T (p.Gln398*) in exon-12 of SLC24A4 by using exome sequencing. Later, its co-segregation within the family was confirmed by Sanger sequencing. The human gene mutation database (HGMD, 2019) has a record of five pathogenic variants in SLC24A4, causing AI phenotype. CONCLUSION: This nonsense sequence variant c.1192C > T (p.Gln398*) is the sixth disease-causing variant in SLC24A4, which extends its mutation spectrum and confirms the role of this gene in the morphogenesis of human tooth enamel. The identified variant highlights the critical role of SLC24A4 in causing a rare AI type in humans.


Assuntos
Amelogênese Imperfeita/genética , Antiporters/genética , Cárie Dentária/genética , Predisposição Genética para Doença , Adulto , Amelogênese Imperfeita/epidemiologia , Amelogênese Imperfeita/patologia , Códon sem Sentido/genética , Cárie Dentária/epidemiologia , Cárie Dentária/patologia , Esmalte Dentário/metabolismo , Éxons/genética , Feminino , Humanos , Masculino , Morfogênese/genética , Paquistão/epidemiologia , Linhagem , Perda de Dente/genética , Perda de Dente/fisiopatologia , Sequenciamento Completo do Exoma , Adulto Jovem
5.
Appl Environ Microbiol ; 86(14)2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32414800

RESUMO

Due to the complex microecology and microenvironment of dental plaque, novel caries prevention strategies require modulating the microbial communities ecologically and reducing the cariogenic properties effectively. Antimicrobial peptide GH12 reduced the lactic acid production and exopolysaccharide (EPS) synthesis of a Streptococcus mutans biofilm and a three-species biofilm in vitro in previous studies. However, the anticaries effects and microecological effects of GH12 remained to be investigated in a complex biofilm model in vitro and an animal caries model in vivo In the present study, GH12 at 64 mg/liter showed the most effective inhibition of lactic acid production, EPS synthesis, pH decline, and biofilm integrity of human dental plaque-derived multispecies biofilms in vitro, and GH12 at 64 mg/liter was therefore chosen for use in subsequent in vitro and in vivo assays. When treated with 64-mg/liter GH12, the dental plaque-derived multispecies biofilms sampled from healthy volunteers maintained its microbial diversity and showed a microbial community structure similar to that of the control group. In the rat caries model with a caries-promoting diet, 64-mg/liter GH12 regulated the microbiota of dental plaque, in which the abundance of caries-associated bacteria was decreased and the abundance of commensal bacteria was increased. In addition, 64-mg/liter GH12 significantly reduced the caries scores of sulcal and smooth surface caries in all locations. In conclusion, GH12 inhibited the cariogenic properties of dental plaque without perturbing the dental plaque microbiota of healthy individuals and GH12 regulated the dysbiotic microbial ecology and arrested caries development under cariogenic conditions.IMPORTANCE The anticaries effects and microecological regulation effects of the antimicrobial peptide GH12 were evaluated systematically in vitro and in vivo GH12 inhibited the cariogenic virulence of dental plaque without overintervening in the microbial ecology of healthy individuals in vitro GH12 regulated the microbial ecology of dental plaque to a certain extent in vivo under cariogenic conditions, increased the proportion of commensal bacteria, and decreased the abundance of caries-associated bacteria. GH12 significantly suppressed the incidence and severity of dental caries in vivo This study thus describes an alternative antimicrobial therapy for dental caries.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Fenômenos Fisiológicos Bacterianos/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Cárie Dentária/prevenção & controle , Placa Dentária/microbiologia , Microbiota/efeitos dos fármacos , Adulto , Animais , Biofilmes/crescimento & desenvolvimento , Cárie Dentária/genética , Feminino , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos , Adulto Jovem
6.
BMC Oral Health ; 20(1): 132, 2020 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-32375748

RESUMO

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.


Assuntos
Amelogenina/genética , Suscetibilidade à Cárie Dentária/genética , Cárie Dentária/genética , Proteínas da Matriz Extracelular/genética , Lactoferrina/genética , Polimorfismo de Nucleotídeo Único/genética , Predisposição Genética para Doença/genética , Genótipo , Humanos
7.
Sci Rep ; 10(1): 6365, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32286402

RESUMO

To construct a saliva-based caries risk assessment model, saliva samples from 176 severe early childhood caries (S-ECC) children and 178 healthy (H) children were screened by real-time PCR-based quantification of the selected species, including Streptococcus mutans, Prevotella pallens, Prevotella denticola and Lactobacillus fermentum. Host factors including caries status, dmft indices, age, gender, and geographic origin were assessed in their influence on abundance of the targeted species, which revealed host caries status as the dominant factor, followed by dmft indices (both P < 0.01). Moreover, levels of S. mutans and P. denticola in the S-ECC group were significantly higher than those in the healthy group (P < 0.001 for S. mutans and P < 0.01 for P. denticola). Interestingly, the co-occurrence network of these targeted species in the S-ECC group differed from that from the healthy group. Finally, based on the combined change pattern of S. mutans and P. pallens, we constructed an S-ECC diagnosis model with an accuracy of 72%. This saliva-based caries diagnosis model is of potential value for circumstances where sampling dental plague is difficult.


Assuntos
Cárie Dentária/genética , Cárie Dentária/microbiologia , Microbiota/genética , Saliva/microbiologia , Criança , Pré-Escolar , Cárie Dentária/epidemiologia , Cárie Dentária/patologia , Feminino , Humanos , Lactobacillus fermentum/genética , Lactobacillus fermentum/patogenicidade , Masculino , Prevotella/genética , Prevotella/patogenicidade , Streptococcus mutans/genética , Streptococcus mutans/patogenicidade
8.
Artigo em Inglês | MEDLINE | ID: mdl-32178265

RESUMO

The ENAM gene is important in the formation of tooth enamel; an alteration can affect the lengthening of the crystals, and the thickness in enamel. The objective was to determine the presence of the single nucleotide variant (SNV) rs12640848 of the ENAM gene in students exposed to different concentrations of fluoride. METHODS: A cross-sectional study was conducted on students exposed to high concentrations of fluoride in the city of Durango which were divided according to the severity of fluorosis and dental caries. Genotype determination was performed by DNA sequencing. The relationship between the severity of dental fluorosis and the allele distribution was determined by the Fisher's exact and Kruskal-Wallis tests. RESULTS: Seventy-one students were included for the sequencing. In the different allelic variations, for the normal genotype AA/TT, the control group presented 75%, for the AG/TC variation, 70.8% in the TF ≤ 4 group, 65% in TF ≥ 5, and 16.7% in TF = 0; with respect to GG/CC variation, 12.5% in TF ≤ 4, 22% in TF ≥ 5, and 8.3% in TF = 0 group (p = 0.000). CONCLUSION: The ENAM gene showed an association in the population exposed to different concentrations of fluoride.


Assuntos
Cárie Dentária , Proteínas da Matriz Extracelular , Fluoretos , Fluorose Dentária , Alelos , Estudos Transversais , Cárie Dentária/genética , Proteínas da Matriz Extracelular/genética , Fluorose Dentária/genética , Humanos , Estudantes
9.
Acta Odontol Scand ; 78(4): 250-255, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32013665

RESUMO

Objectives: Carbonic anhydrase (CA) VI is supposed to take part in pH or buffering capacity regulation, which can influence the caries risk of an individual. Its expression in the saliva can be modified by single nucleotide polymorphism (SNP). The aim was to investigate SNP in the CA VI gene in relation to active dental caries and physiochemical properties of saliva.Materials and methods: One hundred and thirty participants aged 11-16 years were involved. Clinical examinations were carried out using standardized WHO criteria, DMFT/DMFS and white spot lesions score was evaluated. Saliva samples were examined for salivary properties and CA VI concentration. DNA evaluated in the investigation was extracted from the buccal smear. Three SNP within CAVI gene (rs2274327; rs2274328; rs2274333) were selected and genotyping was performed.Results: In the active caries group, the mean CAVI concentration was significantly lower than in caries free group (p = .014). No association between increased or decreased risk of caries and analysed SNPs was found. There were some significant relations concerning SNPs and salivary buffer capacity and flow rate in rs2274327 and rs2274328.Conclusions: Polymorphism in the CAVI gene can affect salivary properties but there is no direct connection with dental caries.


Assuntos
Anidrases Carbônicas/genética , Cárie Dentária/enzimologia , Cárie Dentária/genética , Éxons/genética , Hemoglobina A Glicada/metabolismo , Saliva/metabolismo , Adolescente , Criança , Índice CPO , Humanos , Concentração de Íons de Hidrogênio , Polimorfismo de Nucleotídeo Único/genética
10.
J Dent Res ; 99(3): 264-270, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31905308

RESUMO

Previous studies report that dental caries is partially heritable, but there is uncertainty in the magnitude of genetic effects and little understanding of how genetic factors might influence caries progression or caries subtypes. This study aimed to estimate the relative importance of genetic and environmental factors in the etiology of different caries outcomes using a twin-based design. Analysis included up to 41,678 twins in the Swedish Twin Register aged 7 to 97 y, and dental data were obtained from preexisting dental records. The outcome measures were 1) summary indices of caries experience, 2) parameters representing trajectory in caries progression derived from longitudinal modeling, and 3) caries scores in groups of biologically similar tooth surfaces derived from hierarchical clustering of tooth surfaces (termed caries clusters). Additive genetic factors explained between 49.1% and 62.7% of variation in caries scores and between 50.0% and 60.5% of variation in caries trajectories. Seven caries clusters were identified, which had estimates of heritability lying between 41.9% and 54.3%. Shared environmental factors were important for only some of these clusters and explained 16% of variation in fissure caries in molar teeth but little variation in other clusters of caries presentation. The genetic factors influencing these clusters were only partially overlapping, suggesting that different biological processes are important in different groups of tooth surfaces and that innate liability to some patterns of caries presentation may partially explain why groups of tooth surfaces form clusters within the mouth. These results provide 1) improved quantification of genetic factors in the etiology of caries and 2) new data about the role of genetics in terms of longitudinal changes in caries status and specific patterns of disease presentation, and they may help lay the foundations for personalized interventions in the future.


Assuntos
Cárie Dentária , Dente , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Análise por Conglomerados , Estudos Transversais , Cárie Dentária/epidemiologia , Cárie Dentária/genética , Humanos , Pessoa de Meia-Idade , Dente Molar , Adulto Jovem
11.
J Endod ; 46(1): 3-11.e1, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31843126

RESUMO

INTRODUCTION: Recent studies involving genetic polymorphism and expression have provided information about their role in periapical lesions. This study aimed to evaluate if there is an association between the genetic polymorphism and gene and protein expressions of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in the periapical inflammatory response. METHODS: A systematic review was conducted through a rigorous search in electronic databases as well as a hand search. Two reviewers (κ = 0.90) evaluated the studies considering predetermined eligibility criteria, extracted data for interpretation, and finally used the Strengthening the Reporting of the Genetic Association statement to determine the quality of the scientific evidence. RESULTS: The initial search identified 251 studies. After excluding the duplicates and applying the eligibility criteria, 15 studies were eligible to be assessed in full. Two studies had grade A and 13 grade B quality according to the Strengthening the Reporting of the Genetic Association and were included. The selected studies showed that the periapical lesion tissue samples had a high concentration of MMPs; moreover, there was an expressive decrease in the concentration of MMPs and TIMPs in patients with periapical lesions after mechanical chemical preparation. In relation to genetic polymorphisms, MMP1, MMP2, MMP3, and MMP8 were associated with a higher risk of periapical lesions. Moreover, MMPs 1, 2, 3, 7, 8, 9, 13, 14, 16, and 25 and TIMP 1, 2, 3, and 4 can play an important role in the progression of periapical lesions. CONCLUSIONS: Based on articles with medium to high quality, MMPs and TIMPs are associated with the formation of periapical lesions (PROSPERO number: CDR42018100406).


Assuntos
Cárie Dentária , Metaloproteinase 2 da Matriz , Polimorfismo Genético , Cárie Dentária/genética , Humanos , Metaloproteinase 2 da Matriz/genética
12.
J Indian Soc Pedod Prev Dent ; 38(4): 381-386, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33402621

RESUMO

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.


Assuntos
Cárie Dentária , Streptococcus mutans , Criança , Índice CPO , Cárie Dentária/genética , Suscetibilidade à Cárie Dentária/genética , Proteínas do Esmalte Dentário , Humanos , Polimorfismo Genético , Saliva , Streptococcus mutans/genética
13.
Sci Rep ; 9(1): 19732, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874981

RESUMO

Human microbiomes are predicted to assemble in a reproducible and ordered manner yet there is limited knowledge on the development of the complex bacterial communities that constitute the oral microbiome. The oral microbiome plays major roles in many oral diseases including early childhood caries (ECC), which afflicts up to 70% of children in some countries. Saliva contains oral bacteria that are indicative of the whole oral microbiome and may have the ability to reflect the dysbiosis in supragingival plaque communities that initiates the clinical manifestations of ECC. The aim of this study was to determine the assembly of the oral microbiome during the first four years of life and compare it with the clinical development of ECC. The oral microbiomes of 134 children enrolled in a birth cohort study were determined at six ages between two months and four years-of-age and their mother's oral microbiome was determined at a single time point. We identified and quantified 356 operational taxonomic units (OTUs) of bacteria in saliva by sequencing the V4 region of the bacterial 16S RNA genes. Bacterial alpha diversity increased from a mean of 31 OTUs in the saliva of infants at 1.9 months-of-age to 84 OTUs at 39 months-of-age. The oral microbiome showed a distinct shift in composition as the children matured. The microbiome data were compared with the clinical development of ECC in the cohort at 39, 48, and 60 months-of-age as determined by ICDAS-II assessment. Streptococcus mutans was the most discriminatory oral bacterial species between health and current disease, with an increased abundance in disease. Overall our study demonstrates an ordered temporal development of the oral microbiome, describes a limited core oral microbiome and indicates that saliva testing of infants may help predict ECC risk.


Assuntos
Cárie Dentária/microbiologia , Microbiota , Boca/microbiologia , Saliva/microbiologia , Streptococcus mutans , Pré-Escolar , Cárie Dentária/genética , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Streptococcus mutans/classificação , Streptococcus mutans/genética , Streptococcus mutans/crescimento & desenvolvimento
14.
Adv Exp Med Biol ; 1197: 179-189, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31732942

RESUMO

The genetic basis of oral health has long been theorized, but little information exists on the heritable variance in common oral and dental disease traits explained by the human genome. We sought to add to the evidence base of heritability of oral and dental traits using high-density genotype data in a well-characterized community-based cohort of middle-age adults. We used genome-wide association (GWAS) data combined with clinical and biomarker information in the Dental Atherosclerosis Risk In Communities (ARIC) cohort. Genotypes comprised SNPs directly typed on the Affymetrix Genome-Wide Human SNP Array 6.0 chip with minor allele frequency of >5% (n = 656,292) or were imputed using HapMap II-CEU (n = 2,104,905). We investigated 30 traits including "global" [e.g., number of natural teeth (NT) and incident tooth loss], clinically defined (e.g., dental caries via the DMFS index, periodontitis via the CDC/AAP and WW17 classifications), and biologically informed (e.g., subgingival pathogen colonization and "complex" traits). Heritability (i.e., variance explained; h2) was calculated using Visscher's Genome-wide Complex Trait Analysis (GCTA), using a random-effects mixed linear model and restricted maximum likelihood (REML) regression adjusting for ancestry (10 principal components), age, and sex. Heritability estimates were modest for clinical traits-NT = 0.11 (se = 0.07), severe chronic periodontitis (CDC/AAP) = 0.22 (se = 0.19), WW17 Stage 4 vs. 1/2 = 0.15 (se = 0.11). "High gingival index" and "high red complex colonization" had h2 > 0.50, while a periodontal complex trait defined by high IL-1ß GCF expression and Aggregatibacter actinomycetemcomitans subgingival colonization had the highest h2 = 0.72 (se = 0.32). Our results indicate that all GWAS SNPs explain modest levels of the observed variance in clinical oral and dental measures. Subgingival bacterial colonization and complex phenotypes encompassing both bacterial colonization and local inflammatory response had the highest heritability, suggesting that these biologically informed traits capture aspects of the disease process and are promising targets for genomics investigations, according to the notion of precision oral health.


Assuntos
Cárie Dentária , Estudo de Associação Genômica Ampla , Fenótipo , Cárie Dentária/genética , Cárie Dentária/microbiologia , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética
15.
Arch Oral Biol ; 108: 104522, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31476523

RESUMO

OBJECTIVE: To present a genetic and protein interaction analysis associated with dental caries. MATERIAL AND METHODS: The first step was to conduct a systematic literature review (SLR) through an electronic database search. Case-controls that reported associations between genes and dental caries were the main type of study design used as inclusion criteria, retrieved from the PubMed and the Virtual Health Library databases, comprising the chronological range from 1982 to 2017. The SLR was guided by PRISMA protocol and the methodological quality of the studies was established through Newcastle-Ottawa Scale (NOS). In the second step, the String Protein Interaction (SPI) approach was used to analyze protein interaction (by esyN software) and also the Ingenuity Pathway Analysis (IPA) to check biological pathways associated with dental caries genes. RESULTS: A total of 51 articles were included to perform this SLR, describing a number of 27 genes associated with dental caries development. At the genetic level, 23 genes have at least one other gene with which they interact. The genes TUFT1, VDR, TFIP11, LTF, HLA-DRB1, MMP2, MMP3 and MUC5B were shown to be connected in interactive networks by at least 10 other genes. CONCLUSION: It is essential to apprehend the multifactorial pattern of inheritance in human disease. This study presents pathways which may be directly correlated with several dental caries phenotype and this contributes to a better understanding of this disease, opening up a wider range of biotechnology options for its effective control in the future.


Assuntos
Cárie Dentária , Predisposição Genética para Doença , Proteínas , Estudos de Casos e Controles , Cárie Dentária/genética , Humanos , Fenótipo , Proteínas/fisiologia
16.
Eur J Clin Microbiol Infect Dis ; 38(11): 2005-2019, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31372904

RESUMO

Human oral cavity (mouth) hosts a complex microbiome consisting of bacteria, archaea, protozoa, fungi and viruses. These bacteria are responsible for two common diseases of the human mouth including periodontal (gum) and dental caries (tooth decay). Dental caries is caused by plaques, which are a community of microorganisms in biofilm format. Genetic and peripheral factors lead to variations in the oral microbiome. It has known that, in commensalism and coexistence between microorganisms and the host, homeostasis in the oral microbiome is preserved. Nonetheless, under some conditions, a parasitic relationship dominates the existing situation and the rise of cariogenic microorganisms results in dental caries. Utilizing advanced molecular biology techniques, new cariogenic microorganisms species have been discovered. The oral microbiome of each person is quite distinct. Consequently, commonly taken measures for disease prevention cannot be exactly the same for other individuals. The chance for developing tooth decay in individuals is dependent on factors such as immune system and oral microbiome which itself is affected by the environmental and genetic determinants. Early detection of dental caries, assessment of risk factors and designing personalized measure let dentists control the disease and obtain desired results. It is necessary for a dentist to consider dental caries as a result of a biological process to be targeted than treating the consequences of decay cavities. In this research, we critically review the literature and discuss the role of microbial biofilms in dental caries.


Assuntos
Biofilmes/crescimento & desenvolvimento , Cárie Dentária/microbiologia , Microbiota/fisiologia , Boca/microbiologia , Bactérias/isolamento & purificação , Bactérias/patogenicidade , Cárie Dentária/genética , Cárie Dentária/prevenção & controle , Doenças da Polpa Dentária/genética , Doenças da Polpa Dentária/microbiologia , Doenças da Polpa Dentária/prevenção & controle , Gengiva/microbiologia , Gengiva/fisiologia , Humanos , Doenças Periodontais/genética , Doenças Periodontais/microbiologia , Doenças Periodontais/prevenção & controle , Saliva/química
17.
Nutrients ; 11(7)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31261961

RESUMO

Taste and diet preferences are complex and influenced by both environmental and host traits while affecting both food selection and associated health outcomes. The present study genotyped 94 single nucleotide polymorphisms (SNPs) in previously reported taste and food intake related genes and assessed associations with taste threshold (TT) and preferred intensity (PT) of sweet, sour and bitter, food preferences, habitual diet intake, and caries status in healthy young Swedish men and women (n = 127). Polymorphisms in the GNAT3, SLC2A4, TAS1R1 and TAS1R2 genes were associated with variation in TT and PT for sweet taste as well as sweet food intake. Increasing PT for sweet was associated with increasing preference and intake of sugary foods. Similarly, increasing TT for sour was associated with increasing intake of sour foods, whereas the associations between food preference/intake and TT/PT for bitter was weak in this study group. Finally, allelic variation in the GNAT3, SLC2A2, SLC2A4, TAS1R1 and TAS1R2 genes was associated with caries status, whereas TT, PT and food preferences were not. It was concluded that variations in taste receptor, glucose transporter and gustducin encoding genes are related to taste perception, food preference and intake as well as the sugar-dependent caries disease.


Assuntos
Cárie Dentária/genética , Comportamento Alimentar , Polimorfismo de Nucleotídeo Único , Percepção Gustatória/genética , Paladar/genética , Adolescente , Cárie Dentária/diagnóstico , Feminino , Frequência do Gene , Predisposição Genética para Doença , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 4/genética , Humanos , Masculino , Fenótipo , Receptores Acoplados a Proteínas-G/genética , Fatores de Risco , Suécia , Transducina/genética , Adulto Jovem
18.
Nat Commun ; 10(1): 2773, 2019 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31235808

RESUMO

Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.


Assuntos
Cárie Dentária/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Periodontite/genética , Cárie Dentária/epidemiologia , Genômica , Hereditariedade , Humanos , Análise da Randomização Mendeliana , Periodontite/epidemiologia , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Autorrelato/estatística & dados numéricos
19.
PLoS One ; 14(4): e0214946, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30973902

RESUMO

Smoking is a leading cause of preventable death. The effect of tobacco is even more contundent in people with mental illness and, in general, cigarette smoking addiction is influenced by genetic factors. The opioid system is involved in the mesolimbic reward system, which is of great importance in addictive behaviors, such as smoking and is influenced by genes such as the OPRM1. The aim of this study was to evaluate if selecting a comparison group that include light smokers versus people that never smoked impacts the results of genetic association studies. In addition, to evaluate the genetic association in different groups of smokers by analyzing independent covariates such as mental illness and clinical dental data. All subjects were participants of the Dental Registry and DNA Repository project. Genotyping was carried out using TaqMan chemistry for two markers in OPRM1 (rs553202 and rs7755635). Logistic regression analyses were performed as implemented in PLINK. The established value for alpha was 5%, and the Hardy-Weinberg equilibrium was evaluated by the chi-square test with one degree of freedom for each marker. 1,897 patients were included, which were allocated to eight distinct groups, according to the frequency and quantity of cigarettes smoked and mental illness status. There was no significant association between the two markers in OPRM1 and smoking. When mental illness and dental clinical data (tooth loss, dental caries, and periodontitis) were used as covariates, there were associations between heavy smoking and OPRM1, when non-smokers were used as comparison. We did not have diet or microbiome data to consider for these dental analyses and suggest that these kinds of data should be always incorporated in the future. Significant results were found only when the covariables mental illness and oral clinical data were added to the analysis.


Assuntos
Comportamento Aditivo , Fumar Cigarros , Cárie Dentária , Periodontite , Receptores Opioides mu/genética , Perda de Dente , Adulto , Comportamento Aditivo/genética , Comportamento Aditivo/patologia , Comportamento Aditivo/fisiopatologia , Fumar Cigarros/genética , Fumar Cigarros/patologia , Fumar Cigarros/fisiopatologia , Cárie Dentária/genética , Cárie Dentária/patologia , Cárie Dentária/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Periodontite/genética , Periodontite/patologia , Periodontite/fisiopatologia , Perda de Dente/genética , Perda de Dente/patologia , Perda de Dente/fisiopatologia
20.
Pediatrics ; 143(5)2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31028158

RESUMO

OBJECTIVES: To explore the relative contributions of genetic and environmental influences on dental caries risk and to investigate fetal and developmental risk factors for dental caries. METHODS: We recruited children from 250 twin pregnancies midgestation and collected demographic, health, and phenotypic data at recruitment, 24 and 36 weeks' gestational age, birth and 18 months, and 6 years of age. 25-hydroxyvitamin D was quantified in mothers at 28 weeks' gestation and in infants at birth. Dental caries and enamel defects were measured at six years of age. We compared concordance for the presence of any caries and advanced caries in monozygotic and dizygotic twin pairs. To investigate environmental risk factors for caries, we fitted multiple logistic regression models using generalized estimating equations to adjust for twin correlation. RESULTS: A total of 345 twins underwent dental assessment, with 111 (32.2%) showing signs of any caries and 83 (24.1%) having advanced caries. There was no evidence of higher concordance in monozygotic twins compared with dizygotic twins, with a difference of 0.05 (95% confidence interval -0.14 to 0.25; P = .30) and 0.00 (95% confidence interval -0.26 to 0.26; P = .50) for any caries and advanced caries, respectively, suggesting that environmental factors, rather than genetics, are the predominant determinant of caries risk. After adjusting for potential confounders, lack of community water fluoridation, hypomineralized second primary molars, dichorionic placenta, and maternal obesity were associated with caries. CONCLUSIONS: Environmental rather than genetic factors drive dental caries risk and arise as early as prenatal life.


Assuntos
Cárie Dentária/epidemiologia , Cárie Dentária/genética , Doenças em Gêmeos/epidemiologia , Doenças em Gêmeos/genética , Meio Ambiente , Interação Gene-Ambiente , Criança , Cárie Dentária/sangue , Doenças em Gêmeos/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Gravidez , Estudos Prospectivos , Fatores de Risco , Vitamina D/análogos & derivados , Vitamina D/sangue
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