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1.
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
2.
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
3.
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
4.
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
5.
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
6.
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
7.
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
8.
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
9.
Methods Mol Biol ; 1922: 493-509, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30838596

RESUMO

Oral health and disease are known to be influenced by complex interactions between environmental (e.g., social and behavioral) factors and innate susceptibility. Although the exact contribution of genomics and other layers of "omics" to oral health is an area of active research, it is well established that the susceptibility to dental caries, periodontal disease, and other oral and craniofacial traits is substantially influenced by the human genome. A comprehensive understanding of these genomic factors is necessary for the realization of precision medicine in the oral health domain. To aid in this direction, the advent and increasing affordability of high-throughput genotyping has enabled the simultaneous interrogation of millions of genetic polymorphisms for association with oral and craniofacial traits. Specifically, genome-wide association studies (GWAS) of dental caries and periodontal disease have provided initial insights into novel loci and biological processes plausibly implicated in these two common, complex, biofilm-mediated diseases. This paper presents a summary of protocols, methods, tools, and pipelines for the conduct of GWAS of dental caries, periodontal disease, and related traits. The protocol begins with the consideration of different traits for both diseases and outlines procedures for genotyping, quality control, adjustment for population stratification, heritability and association analyses, annotation, reporting, and interpretation. Methods and tools available for GWAS are being constantly updated and improved; with this in mind, the presented approaches have been successfully applied in numerous GWAS and meta-analyses among tens of thousands of individuals, including dental traits such as dental caries and periodontal disease. As such, they can serve as a guide or template for future genomic investigations of these and other traits.


Assuntos
Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Técnicas de Genotipagem/métodos , Odontopatias/genética , DNA/genética , DNA/isolamento & purificação , Cárie Dentária/genética , Genoma Humano , Humanos , Doenças Periodontais/genética , Fenótipo , Software
10.
J Int Med Res ; 47(4): 1696-1704, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30803280

RESUMO

OBJECTIVE: To 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. METHODS: This 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. RESULTS: A 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). CONCLUSION: The IL1B rs1143627C/T polymorphism may be associated with dental caries susceptibility in children from northwest China.


Assuntos
Cárie Dentária/genética , Proteínas do Esmalte Dentário/genética , Proteínas da Matriz Extracelular/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-10/genética , Interleucina-1beta/genética , Metaloproteinase 13 da Matriz/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Criança , Cárie Dentária/patologia , Feminino , Seguimentos , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Prognóstico
11.
Caries Res ; 53(1): 49-59, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29898447

RESUMO

Erosive tooth wear is defined as irreversible loss of dental tissues due to intrinsic or extrinsic acids, exacerbated by mechanical forces. Recent studies have suggested a higher prevalence of erosive tooth wear in males, as well as a genetic contribution to susceptibility to erosive tooth wear. Our aim was to examine erosive tooth wear by performing a genome-wide association study (GWAS) in a sample of the Northern Finland Birth Cohort 1966 (n = 1,962). Erosive tooth wear was assessed clinically using the basic erosive wear examination. A GWAS was performed for the whole sample as well as separately for males and females. We identified one genome-wide significant signal (rs11681214) in the GWAS of the whole sample near the genes PXDN and MYT1L. When the sample was stratified by sex, the strongest genome-wide significant signals were observed in or near the genes FGFR1, C8orf86, CDH4, SCD5, F2R, and ING1. Additionally, multiple suggestive association signals were detected in all GWASs performed. Many of the signals were in or near the genes putatively related to oral environment or tooth development, and some were near the regions considered to be associated with dental caries, such as 2p24, 4q21, and 13q33. Replications of these associations in other samples, as well as experimental studies to determine the biological functions of associated genetic variants, are needed.


Assuntos
Erosão Dentária/epidemiologia , Erosão Dentária/genética , Adulto , Estudos de Coortes , Cárie Dentária/genética , Feminino , Finlândia/epidemiologia , Genes , Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prevalência , Fatores de Risco , Fatores Sexuais , Atrito Dentário
12.
Int J Paediatr Dent ; 29(1): 29-35, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30341791

RESUMO

BACKGROUND: Oestrogen (ES) and growth hormone (GH) are hormones that may have a role in caries aetiology and developmental defects of enamel (DDE) since their receptors (ERs and GHR) are expressed during amelogenesis. AIM: To evaluate whether genetic polymorphisms in the genes that codify the ERα (ESR1) and GHR are associated with caries experience and DDE in children. DESIGN: Two hundred and sixteen children of both genders, aged 9-12 years, were examined and classified according to caries and DDE phenotype. Genomic DNA was extracted from buccal cells in saliva. Genetic polymorphisms in ERS1 (rs1884051 and rs12154178) and GHR (rs297305, rs2940913, rs2910875, and rs1509460) were genotyped using TaqMan chemistry. Data were analysed by PLINK, while the chi-square test was used to compare allele and genotype distributions (alpha of 5%). RESULTS: A total of 131 children (60.7%) had caries experience, and 43 (19.9%) presented DDE. Genotype and allele distributions were not associated with caries experience (P > 0.05). Genotype and allele distributions between DDE, affected and unaffected, were associated with the polymorphism rs12154178 in ESR1 (P = 0.01 and P = 0.001, respectively) and with the polymorphism rs1509460 in GHR (P = 0.05 and P = 0.02, respectively). CONCLUSIONS: Genetic polymorphisms in ERS1 (rs12154178) and GHR (rs1509460) are associated with DDE.


Assuntos
Cárie Dentária/genética , Esmalte Dentário/anormalidades , Receptor alfa de Estrogênio/genética , Polimorfismo Genético , Receptores da Somatotropina/genética , Criança , Feminino , Genótipo , Humanos , Masculino
13.
Caries Res ; 53(1): 60-64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29902796

RESUMO

This case-control study aimed to investigate the effect of rs11003125 in dental caries. For this purpose, a total number of 404 individuals - from Fars Province in Iran - were studied. The technique of this research was the tetra-primer amplification-refractory mutation system (ARMS)-PCR. Dental caries prevalence among the 404 individuals was assessed by counting the number of decayed, missing, and filled teeth. In this research, individuals were divided into two groups: cases (n = 238) and controls (n = 166), and the peripheral blood samples were used to extract the genomic DNA. For genotyping of DNA, the tetra-primer ARMS-PCR method was conducted using specific primer pairs. While examining MBL2 rs11003125 polymorphism, we found significant differences in the genotype frequencies between the case and the control group. The pooled estimates indicated that the GG and GC genotypes of MBL2 rs11003125 polymorphism significantly increased, and therefore caries risk (OR = 2.40, 95% CI = 1.31-4.40, p = 0.004) under the dominant model. These findings suggested that polymorphism in MBL2 gene was associated with dental caries in Iranian adults. Further verification is needed with more ethnic groups and larger sample sizes to determine whether rs11003125 polymorphism is related to dental caries in other regions or not.


Assuntos
Cárie Dentária/epidemiologia , Cárie Dentária/genética , Lectina de Ligação a Manose/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Prevalência , Risco , Adulto Jovem
14.
Sci Rep ; 8(1): 14010, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30228377

RESUMO

Dental caries is caused by acids released from bacterial biofilms. However, the in vivo formation of initial biofilms in relation to caries remains largely unexplored. The aim of this study was to compare the oral microbiome during the initial phase of bacterial colonization for individuals with (CC) and without (NC) cavitated dentin caries lesions. Bovine enamel slabs on acrylic splints were worn by the volunteers (CC: 14, NC: 13) for in situ biofilm formation (2 h, 4 h, 8 h, 1 ml saliva as reference). Sequencing of the V1/V2 regions of the 16S rRNA gene was performed (MiSeq). The relative abundances of individual operational taxonomic units (OTUs) were compared between samples from the CC group and the NC group. Random forests models were furthermore trained to separate the groups. While the overall heterogeneity did not differ substantially between CC and NC individuals, several individual OTUs were found to have significantly different relative abundances. For the 8 h samples, most of the significant OTUs showed higher relative abundances in the CC group, while the majority of significant OTUs in the saliva samples were more abundant in the NC group. Furthermore, using OTU signatures enabled a separation between both groups, with area-under-the-curve (AUC) values of ~0.8. In summary, the results suggest that initial oral biofilms provide the potential to differentiate between CC and NC individuals.


Assuntos
Biofilmes/crescimento & desenvolvimento , Biomarcadores/análise , Cárie Dentária/microbiologia , Esmalte Dentário/microbiologia , Microbiota/genética , Boca/microbiologia , Saliva/microbiologia , Adulto , Animais , Estudos de Casos e Controles , Bovinos , Cárie Dentária/genética , Cárie Dentária/patologia , Esmalte Dentário/metabolismo , Esmalte Dentário/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Adulto Jovem
15.
Oral Dis ; 24(8): 1545-1553, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29989276

RESUMO

OBJECTIVE: Dental caries is related to cariogenic bacteria, salivary components, oral hygiene and host susceptibility. Lactoferrin is an important antimicrobial glycoprotein in saliva; however, the role of the LTF gene in caries susceptibility is unclear. We investigated the association between LTF polymorphisms and the severity of caries. DESIGN: Our study included 910 healthy paediatric subjects (aged 24-48 months) categorised into three groups: 403 with no caries or white-spot lesions; 230 with moderate caries (8 ≤ dmft ≤ 12); and 277 with severe caries (13 ≤ dmft ≤ 20). Information regarding the subjects' oral habits was gathered using questionnaires. The LTF rs1126477 and rs1126478 polymorphism alleles were genotyped by Sanger sequencing. RESULTS: The three groups showed no significant differences in LTF polymorphisms alleles, genotypes or haplotypes distribution. Multifactor dimensionality reduction analysis showed that the interactions between breastfeeding for a duration >24 months, night feeding >24 months and high frequency of sweet food intake increased the risk of caries (p = 0.0014); however, we detected no interaction effect between the LTF polymorphisms and oral habits on caries susceptibility. CONCLUSIONS: The LTF rs1126477 and rs1126478 polymorphisms showed no association with the different levels of caries risk in our Chinese paediatric cohort.


Assuntos
Cárie Dentária/genética , Lactoferrina/genética , Dente Decíduo , Pré-Escolar , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Polimorfismo Genético , Índice de Gravidade de Doença
16.
Hum Mol Genet ; 27(17): 3113-3127, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-29931343

RESUMO

Prior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from nine contributing centres. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage and the results were combined using fixed-effects meta-analysis. Analysis included up to 19 003 individuals (7530 affected) for primary teeth and 13 353 individuals (5875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth [intronic within ALLC, odds ratio (OR) 0.85, effect allele frequency (EAF) 0.60, P 4.13e-8] and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, P 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low [h2 of 1% (95% CI: 0%: 7%) and 6% (95% CI 0%: 13%) for primary and permanent dentitions, respectively] compared with corresponding within-study estimates [h2 of 28% (95% CI: 9%: 48%) and 17% (95% CI: 2%: 31%)] or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Biomarcadores/análise , Cárie Dentária/genética , Dentição Permanente , Estudo de Associação Genômica Ampla/métodos , Fosfoproteínas/genética , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Fenótipo
17.
BMC Oral Health ; 18(1): 98, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29859070

RESUMO

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


Assuntos
Suscetibilidade à Cárie Dentária/genética , Cárie Dentária/genética , Adolescente , Adulto , Criança , Pré-Escolar , Cromossomos Humanos/genética , Estudo de Associação Genômica Ampla , Humanos , Iowa , Escore Lod , Pessoa de Meia-Idade , Pennsylvania , Fenótipo , Polimorfismo de Nucleotídeo Único , West Virginia , Adulto Jovem
18.
Arch Oral Biol ; 92: 1-7, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29727722

RESUMO

OBJECTIVE: This replication study aimed to evaluate an association between caries experience and polymorphisms in DEFB1 and miRNA202 in two different Brazilian groups. DESIGN: The population consisted in 312 Brazilian children. Genomic DNA for was extracted from buccal cells isolated from saliva. The genotyping analysis of the polymorphisms in DEFB1 and miRNA202 was performed by real-time polymerase chain reactions. The associations between caries experience, genotype and allele distribution was performed, with an alpha of 0.05. RESULTS: A statistical significant difference was observed between allele distribution and the polymorphism rs12355840 in the miRNA202 for permanent dentition in the Manaus group, in which individuals that carry the allele C had almost three times more chance to have caries (p = .021; OR = 2.7, 95% CI = 1.1-6.7). In the Ribeirão Preto group there was a statistical significant difference for the polymorphism rs11362 in the DEFB1 for both dentition in alleles (p = .043) and genotype (p = .020) distributions. The T allele increased in two times the chance to have caries (OR = 2.03; 95% CI = 1.05-4.07). CONCLUSION: In conclusion, the allelic distribution of the polymorphism rs12355840 in miRNA202 was associated with caries experience in the Manaus group. In the Ribeirão Preto group, the allelic and genotypic distributions in the polymorphism rs11362 in DEFB1 were associated with caries experience.


Assuntos
Cárie Dentária/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , beta-Defensinas/genética , Alelos , Brasil , Criança , Feminino , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase em Tempo Real
19.
Sci Rep ; 8(1): 7267, 2018 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-29740156

RESUMO

Oral microbiome is potentially correlated with many diseases, such as dental caries, periodontitis, oral cancer and some systemic diseases. Twin model, as an effective method for studying human microbiota, is widely used in research of relationship between oral microbiota and dental caries. However, there were few researches focusing on caries discordant twins. In this study, in vitro assays were conducted combined with 16S rRNA sequencing analysis on oral microbiota sampled from twins who presented discordant caries experience and mice model was developed as well. Results showed that oral microbiota from caries-active twin possessed higher metabolic activity and produced more lactic production. 16S rRNA sequencing analysis showed that more than 80% of family taxa could be transferred into gnotobiotic-mice. Key caries-associated genera were significantly different between twins and the same difference in genus level could be found in mice as well (p < 0.05). This study suggested that oral microbiota of twins could be distinguished from each other despite the similarities in genetic make-up, living environment, and lifestyle. The difference in microbiota was applied to develop a mice model which may facilitate the investigation of core microbiota of dental caries.


Assuntos
Cárie Dentária/microbiologia , Microbiota/genética , Boca/microbiologia , Periodontite/genética , Animais , Bactérias/genética , Bactérias/patogenicidade , Cárie Dentária/genética , Cárie Dentária/patologia , Placa Dentária/genética , Placa Dentária/microbiologia , Vida Livre de Germes/genética , Humanos , Camundongos , Periodontite/microbiologia , RNA Ribossômico 16S/genética , Gêmeos Monozigóticos/genética
20.
Stomatologiia (Mosk) ; 97(2): 27-31, 2018.
Artigo em Russo | MEDLINE | ID: mdl-29795101

RESUMO

The aim of the study was to evaluate the allelic polymorphisms kallikrein-4 (KLK-4) gene at the mutant points: G2664153A and G2142A in pregnant women under and over 30 of age. In pregnant women with KLK-4 gene polymorphisms A/A and G/A genotypes the rate of tooth decay growth increases in spite of applying the ternary calcium-phosphate-fluoride-containing gel. This genotype is also associates with unfavorable alteration of such oral fluid indicators as pH, concentrations of inorganic phosphorus, the active concentrations of calcium and potassium, as well as the ratio of total calcium and phosphorus concentrations, the active concentrations of electrolytes, and demineralizing activity of oral fluid.


Assuntos
Cárie Dentária , Calicreínas , Complicações na Gravidez , Cálcio/metabolismo , Cárie Dentária/genética , Feminino , Humanos , Concentração de Íons de Hidrogênio , Calicreínas/genética , Fósforo/metabolismo , Polimorfismo Genético , Gravidez , Complicações na Gravidez/genética
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