Aquaporins' Influence on Different Dental Erosive Wear Phenotypes in Humans.

Dental erosive wear is a multifactorial condition of high prevalence. Nowadays, there is an emphasis on discovering individual genetic predisposition for the development of this condition. Aquaporins (AQPs) are water channel proteins expressed in salivary glands, as well as during tooth development. They are involved in salivary secretion and composition and linked to physiological protection of the oral cavity. The aim of this study was to explore the relationship between different dental erosive wear phenotypes, AQP genes, and selected environmental factors. Data from 705 dental patients were used to investigate the association between dental erosive wear phenotypes and AQPs' single-nucleotide variants. Phenotypes were further analyzed considering diet and oral hygiene data, using logistic regression analysis, as implemented in PLINK, with the assumption that dental erosive wear is a complex gene-environment model. Associations were found between severe erosive tooth wear and rs2878771 (AQP2) for the genotypic (p = 0.02) and dominant (p = 0.03) models, and rs3736309 (AQP5) for the allelic model (p = 0.02). Logistic regression analyses, after implementing the Bonferroni correction, showed that several significant associations were present when covariates were included, suggesting that a strong environmental component is present. Our results show that dental erosive wear establishes under a gene-environmental complex model.

Are mTOR and Endoplasmic Reticulum Stress Pathway Genes Associated with Oral and Bone Diseases?

The purpose of this cohort study was to identify associations between combined oral and bone disease phenotypes and genes present in cell regulatory pathways. The studied pathways play important roles in cellular growth, proliferation, differentiation, and homeostasis. DNA samples extracted from whole saliva of 3,912 individuals were genotyped and these data analyzed according to dental caries experience, periapical lesions, periodontitis, osteoporosis, or temporomandibular joint discomfort. Samples were obtained from the Dental Registry and DNA Repository project at the University of Pittsburgh. Twenty-seven polymorphisms in eight genes related to mTOR or endoplasmic reticulum stress pathways were selected for genotyping. Allele frequencies and Hardy-Weinberg equilibrium were calculated. Analyses were performed comparing genotypes between affected and unaffected individuals for each phenotype, as well as for the associated phenotypes combined. For all analyses, we used the software PLINK with an alpha of 0.002. Borderline associations with multiple variants of several genes were found, suggesting that both pathways may be involved in the susceptibility to multiple conditions affecting the oral cavity and bones. When combining patients that had concomitant dental caries, periodontitis, and periapical pathology, several markers in RHEB showed statistically significant association. Multiple conditions affecting bone and teeth (i.e., dental caries, periodontitis, periapical lesion formation, and osteoporosis) appear to share similar underlying genetic etiological factors, which allow us to hypothesize that instead of individually, they should be studied in conjunction in human populations.

Redefining the Phenotype of Dental Caries.

Dental caries is a multifactorial infectious disease and a major public health problem estimated to affect 60-90% of school children as well as a vast number of adults. The aim of this work was to define patterns of progression of the disease based on longitudinal data in contrast to using a cross-sectional assessment. dmft/DMFT scores were collected at ages 5, 12, 14, 16, 17, and 18 from 876 individuals. We tested our newly defined phenotypes for association with genetic variants in genes shown to be associated with caries. We generated genotyping data using Taqman chemistry in markers of genes involved in processes such as enamel formation and salivary contributions. Kallikrein 4 (KLK4) was found to show a significant association with the created phenotypes (p = 0.0008 in a recessive model for low caries experience in the primary dentition vs. high caries experience in the primary dentition, and p = 0.0004 in a recessive model for caries free primary dentition vs. high caries experience in the primary dentition).

Early childhood caries is associated with genetic variants in enamel formation and immune response genes.

Early childhood caries (ECC) is a chronic, infectious disease that affects the primary dentition of young children. It is the result of an imbalance of risk factors and protective factors that influence the disease. The aim of this study was to assess genetic and environmental factors that may contribute to ECC. Two hundred and fifty-nine unrelated children were evaluated using a cross-sectional design. Data on oral habits were obtained through a questionnaire, and caries experience data were collected by clinical examination. Twenty-three markers in 10 genes were studied. Genotyping of the selected polymorphisms was carried out by real-time PCR. Regression analyses were performed comparing individuals with and without caries experience. Of 259 subjects, 123 were caries free. The genotype TT in ALOX15 (rs7217186) was a risk factor for ECC, whereas the genotypes GG in ENAM (rs1264848), AG and GG in KLK4 (rs198968), CT in LTF (rs4547741), and GG in TUFT1 (rs3790506) were protective for EEC. In conclusion, environmental factors and gene interactions can act as protective or risk factors for ECC. These factors together contribute to the presence and severity of the disease.

Role of estrogen related receptor beta (ESRRB) in DFN35B hearing impairment and dental decay.

BACKGROUND: Congenital forms of hearing impairment can be caused by mutations in the estrogen related receptor beta (ESRRB) gene. Our initial linkage studies suggested the ESRRB locus is linked to high caries experience in humans. METHODS: We tested for association between the ESRRB locus and dental caries in 1,731 subjects, if ESRRB was expressed in whole saliva, if ESRRB was associated with the microhardness of the dental enamel, and if ESRRB was expressed during enamel development of mice. RESULTS: Two families with recessive ESRRB mutations and DFNB35 hearing impairment showed more extensive dental destruction by caries. Expression levels of ESRRB in whole saliva samples showed differences depending on sex and dental caries experience. CONCLUSIONS: The common etiology of dental caries and hearing impairment provides a venue to assist in the identification of individuals at risk to either condition and provides options for the development of new caries prevention strategies, if the associated ESRRB genetic variants are correlated with efficacy.

Intraoral metal contact allergy as a possible risk factor for oral squamous cell carcinoma.

OBJECTIVES: Intraoral exposure to dental restorations can cause contact allergy that may induce carcinogenesis. We investigated the relationship of intraoral metal contact allergy to epithelial carcinogenesis. METHODS: The prevalence of positive patch test reactions to dental restoration metals in 65 prospectively enrolled patients with newly or previously diagnosed oral squamous cell carcinoma (SCC) was compared to that in 48 control patients. The relative risk of oral SCC was estimated by calculating odds ratios for exposure to dental metals resulting in allergy. RESULTS: Of the 65 patients with oral SCC, 34% were allergic to at least 1 adjacent metal. They were 1.57 times as likely as control patients to have metal contact allergy (odds ratio, 1.57; 95% confidence interval, 0.65 to 3.80) and more than 3 times as likely to react to mercury (odds ratio, 3.20; 95% confidence interval, 0.42 to 33.20). CONCLUSIONS: Patients with oral SCC who have metal dental restorations should undergo patch testing and possible removal of the restorations if their reactions are positive.