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1.
PLoS One ; 10(12): e0143068, 2015.
Article in English | MEDLINE | ID: mdl-26630491

ABSTRACT

Aquaporins (AQP) are water channel proteins and the genes coding for AQP2, AQP5, and AQP6 are clustered in 12q13. Since AQP5 is expressed in serous acinar cells of salivary glands, we investigated its involvement in caries. DNA samples from 1,383 individuals from six groups were studied. Genotypes of eight single nucleotide polymorphisms covering the aquaporin locus were tested for association with caries experience. Interaction with genes involved in enamel formation was tested. The association between enamel microhardness at baseline, after creation of artificial caries lesion, and after exposure to fluoride and the genetic markers in AQP5 was tested. Finally, AQP5 expression in human whole saliva, after exposure to fluoride in a mammary gland cell line, which is known to express AQP5, and in Wistar rats was also verified. Nominal associations were found between caries experience and markers in the AQP5 locus. Since these associations suggested that AQP5 may be inhibited by levels of fluoride in the drinking water that cause fluorosis, we showed that fluoride levels above optimal levels change AQP5 expression in humans, cell lines, and rats. We have shown that AQP5 is involved in the pathogenesis of caries and likely interacts with fluoride.


Subject(s)
Aquaporin 5/metabolism , Dental Caries/metabolism , Fluorides/metabolism , Adolescent , Adult , Animals , Aquaporin 5/genetics , Cell Line, Tumor , Child , Child, Preschool , Dental Caries/genetics , Female , Genetic Markers/genetics , Genotype , Humans , Male , Mammary Glands, Human/metabolism , Middle Aged , Polymorphism, Single Nucleotide/genetics , Rats , Rats, Wistar , Saliva/metabolism , Young Adult
2.
J Oral Maxillofac Surg ; 71(7): 1202-8, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23522767

ABSTRACT

Follicular lymphoid hyperplasia of the palate is a benign lymphoproliferative lesion of unknown pathogenesis. It presents usually in female patients as a painless, firm, well-demarcated, usually nonulcerated, slow-growing lesion on the palate that histopathologically may resemble a lymphoma. The authors describe a patient with this condition that was successfully treated with intralesional steroid injections. Previously reported cases were reviewed to assess the results of various treatment modalities and disease-free outcome. A nonsurgical approach to the management of follicular lymphoid hyperplasia may have better patient acceptance and satisfaction without recurrence.


Subject(s)
Glucocorticoids/administration & dosage , Immunosuppressive Agents/administration & dosage , Lymphoproliferative Disorders/drug therapy , Mouth Diseases/drug therapy , Palate, Hard/drug effects , Triamcinolone Acetonide/administration & dosage , Anesthetics, Local/administration & dosage , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Injections, Intralesional , Lidocaine/administration & dosage , Lymphoproliferative Disorders/pathology , Middle Aged , Mouth Diseases/pathology , Mouth Mucosa/drug effects , Mouth Mucosa/pathology , Palate, Hard/pathology , Salivary Glands, Minor/drug effects , Salivary Glands, Minor/pathology
3.
BMC Oral Health ; 12: 57, 2012 Dec 21.
Article in English | MEDLINE | ID: mdl-23259602

ABSTRACT

BACKGROUND: Over 90% of adults aged 20 years or older with permanent teeth have suffered from dental caries leading to pain, infection, or even tooth loss. Although caries prevalence has decreased over the past decade, there are still about 23% of dentate adults who have untreated carious lesions in the US. Dental caries is a complex disorder affected by both individual susceptibility and environmental factors. Approximately 35-55% of caries phenotypic variation in the permanent dentition is attributable to genes, though few specific caries genes have been identified. Therefore, we conducted the first genome-wide association study (GWAS) to identify genes affecting susceptibility to caries in adults. METHODS: Five independent cohorts were included in this study, totaling more than 7000 participants. For each participant, dental caries was assessed and genetic markers (single nucleotide polymorphisms, SNPs) were genotyped or imputed across the entire genome. Due to the heterogeneity among the five cohorts regarding age, genotyping platform, quality of dental caries assessment, and study design, we first conducted genome-wide association (GWA) analyses on each of the five independent cohorts separately. We then performed three meta-analyses to combine results for: (i) the comparatively younger, Appalachian cohorts (N = 1483) with well-assessed caries phenotype, (ii) the comparatively older, non-Appalachian cohorts (N = 5960) with inferior caries phenotypes, and (iii) all five cohorts (N = 7443). Top ranking genetic loci within and across meta-analyses were scrutinized for biologically plausible roles on caries. RESULTS: Different sets of genes were nominated across the three meta-analyses, especially between the younger and older age cohorts. In general, we identified several suggestive loci (P-value ≤ 10E-05) within or near genes with plausible biological roles for dental caries, including RPS6KA2 and PTK2B, involved in p38-depenedent MAPK signaling, and RHOU and FZD1, involved in the Wnt signaling cascade. Both of these pathways have been implicated in dental caries. ADMTS3 and ISL1 are involved in tooth development, and TLR2 is involved in immune response to oral pathogens. CONCLUSIONS: As the first GWAS for dental caries in adults, this study nominated several novel caries genes for future study, which may lead to better understanding of cariogenesis, and ultimately, to improved disease predictions, prevention, and/or treatment.


Subject(s)
Dental Caries Susceptibility/genetics , Dental Caries/genetics , Genome-Wide Association Study , MAP Kinase Signaling System/genetics , Wnt Signaling Pathway/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Chromosomes, Human/genetics , DMF Index , Dentition, Permanent , Humans , Middle Aged , Young Adult
4.
ISRN Dent ; 2011: 543561, 2011.
Article in English | MEDLINE | ID: mdl-21731912

ABSTRACT

Caries is a multifactorial disease, and studies aiming to unravel the factors modulating its etiology must consider all known predisposing factors. One major factor is bacterial colonization, and Streptococcus mutans is the main microorganism associated with the initiation of the disease. In our studies, we have access to DNA samples extracted from human saliva and blood. In this report, we tested a real-time PCR assay developed to detect copies of genomic DNA from Streptococcus mutans in 1,424 DNA samples from humans. Our results suggest that we can determine the presence of genomic DNA copies of Streptococcus mutans in both DNA samples from caries-free and caries-affected individuals. However, we were not able to detect the presence of genomic DNA copies of Streptococcus mutans in any DNA samples extracted from peripheral blood, which suggests the assay may not be sensitive enough for this goal. Values of the threshold cycle of the real-time PCR reaction correlate with higher levels of caries experience in children, but this correlation could not be detected for adults.

5.
Eur J Dent ; 3(4): 297-303, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19826602

ABSTRACT

OBJECTIVES: There is evidence of association between systemic diseases and oral conditions, although it is not clear if these are direct or mediated by underlying factors such as health behaviors. The aim of this work was to evaluate whether self-reported systemic diseases were associated with caries experience. METHODS: Medical history data and caries experience (DMFT and DMFS; Decayed, Missing due to caries, Filled Teeth/Surface) were obtained from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository. Information on 318 subjects (175 females and 143 males) was evaluated. Regression analysis was used to test for association between caries experience and disease status. RESULTS: The stronger associations were found between caries experience and asthma and epilepsy. With respect to asthma, DMFT above 15 (R(2) = 0.04) and DMFS above 50 (R(2) = 0.02) were associated. After controlling for gender differences in asthma, the associations remained strong (R(2) = 0.05 for both DMFT and DMFS). For epilepsy, DMFT above 15 (R(2) = 0.18) and DMFS above 50 (R(2) = 0.14) were associated. CONCLUSIONS: Asthma and epilepsy are associated with higher caries experience.

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