Search

Dental caries continues to be the most common chronic disease in children today. Despite the substantial involvement of genetics in the process of caries development, the specific genes contributing to dental caries remain largely unknown. We performed separate genome-wide association studies of smooth and pit-and-fissure tooth surface caries experience in the primary dentitions of self-reported white children in two samples from Iowa and rural Appalachia. In total, 1,006 children (ages 3-12 years) were included for smooth surface analysis, and 979 children (ages 4-14 years) for pit-and-fissure surface analysis. Associations were tested for more than 1.2 million single nucleotide polymorphisms, either genotyped or imputed. We detected genome-wide significant signals in KPNA4 (p value = 2.0E-9), and suggestive signals in ITGAL (p value = 2.1E-7) and PLUNC family genes (p value = 2.0E-6), thus nominating these novel loci as putative caries susceptibility genes. We also replicated associations observed in previous studies for MPPED2 (p value = 6.9E-6), AJAP1 (p value = 1.6E-6) and RPS6KA2 (p value = 7.3E-6). Replication of these associations in additional samples, as well as experimental studies to determine the biological functions of associated genetic variants, are warranted. Ultimately, efforts such as this may lead to a better understanding of caries etiology, and could eventually facilitate the development of new interventions and preventive measures., (© 2014 S. Karger AG, Basel.)

Dental caries remains the most common chronic childhood disease. Despite strong evidence of genetic components, there have been few studies of candidate genes and caries. In this analysis we tried to assess genetic and environmental factors contributing to childhood caries in the Iowa Fluoride Study. Environmental factors (age, sex, race, tooth-brushing frequencies and water fluoride level) and three dental caries scores (d(2)fs-total, d(2)fs-pit/fissure, and d(2)fs-smooth surface) were assessed in 575 unrelated children (mean age 5.2 years). Regression analyses were applied to assess environmental correlates. The Family-Based Association Test was used to test genetic associations for 23 single nucleotide polymorphism (SNP) markers in 7 caries candidate genes on 333 Caucasian parent-child trios. We evaluated the associations between caries status and the level of both single and multiple SNPs (haplotype) respectively. Permutation procedure was performed for correction of inflated type I errors due to multiple testing. Age, tooth-brushing frequency and water fluoride level were significantly correlated to at least one carious score. Caries on pit and fissure surfaces was substantially higher than on smooth surfaces (61 vs. 39%). SNPs in three genes (DSPP, KLK4 and AQP5) showed consistent associations with protection against caries. Of note, KLK4 and AQP5 were also highlighted by subsequent haplotype analysis. Our results support the concept that genes can modify the susceptibility of caries in children. Replication analysis in independent cohorts is highly needed in order to verify the validity of our findings., (Copyright © 2012 S. Karger AG, Basel.)

Background/aims: Currently available techniques for fluoride analysis are not standardized. Therefore, this study was designed to develop standardized methods for analyzing fluoride in biological and nonbiological samples used for dental research., Methods: A group of nine laboratories analyzed a set of standardized samples for fluoride concentration using their own methods. The group then reviewed existing analytical techniques for fluoride analysis, identified inconsistencies in the use of these techniques and conducted testing to resolve differences. Based on the results of the testing undertaken to define the best approaches for the analysis, the group developed recommendations for direct and microdiffusion methods using the fluoride ion-selective electrode., Results: Initial results demonstrated that there was no consensus regarding the choice of analytical techniques for different types of samples. Although for several types of samples, the results of the fluoride analyses were similar among some laboratories, greater differences were observed for saliva, food and beverage samples. In spite of these initial differences, precise and true values of fluoride concentration, as well as smaller differences between laboratories, were obtained once the standardized methodologies were used. Intraclass correlation coefficients ranged from 0.90 to 0.93, for the analysis of a certified reference material, using the standardized methodologies., Conclusion: The results of this study demonstrate that the development and use of standardized protocols for F analysis significantly decreased differences among laboratories and resulted in more precise and true values., (2010 S. Karger AG, Basel.)

The purpose of this study was to assess the longitudinal relationships between enamel hypoplasia and caries experience of primary second molars. The study sample was 491 subjects who received dental examinations at both age 5 and 9 by the calibrated examiners. Four primary second molars (n = 1,892) were scored for the presence of enamel hypoplasia for each participant. Caries presence and number of decayed and filled surfaces (dfs) were determined at age 5 and 9. The relationships between enamel hypoplasia and caries experience were assessed. Among primary second molars, 3.9% of children and 1.7% of primary second molars had enamel hypoplasia. At age 5, 36.8% of children with hypoplasia had caries, while 16.9% of children without enamel hypoplasia had caries. At age 9, the corresponding numbers were 52.6% for children with hypoplasia and 34.5% for children without hypoplasia, respectively. At the tooth level, for age 5, 28.1% of teeth with hypoplasia had caries (mean dfs = 0.40), and 7.6% of teeth without hypoplasia had caries (mean dfs = 0.11). At age 9, the corresponding numbers were 41.9% (mean dfs = 0.76) for teeth with hypoplasia and 18.3% (mean dfs = 0.34) for teeth without hypoplasia. In multivariable logistic regression analyses, teeth of subjects with enamel hypoplasia had a significantly higher risk for caries at age 5 and 9 after controlling for other risk factors. Enamel hypoplasia appears to be a significant risk factor for caries and should be considered in caries risk assessment.

Objective: To examine levels of fluorosis among children in two Canadian communities exposed to fluoride., Background: One community had discontinued fluoride, the other had maintained it. Water supplies, however, were fluoridated for all the children when their esthetically important teeth were mineralized., Methods: We examined 8,277 children to assess Thystrup-Fejerskov Index (TFI) scores. Multivariate Poisson regression models were used to identify the relationship between TFI and water fluoride status, age, gender, SES, and dietary and fluoride exposure histories (supplements, rinses, toothpaste amount, tooth brushing frequency, and tooth brushing starting age). Parent(s) completed questionnaires., Results: Overall, levels of fluorosis were low to mild, with residents of the fluoridation-ended communities having marginally higher TFI scores than those of the still-fluoridated community. Females had higher TFI scores than males. Children aged 10 years or more had higher TFI scores than younger children. Consuming bottled water between birth and 6 months of age was protective. Exposure to fluoridation technologies was consistently associated with fluorosis experience. Children who began brushing with fluoride toothpaste between their first and second birthdays had higher TFI scores than those who began between their second and third birthdays, regardless of daily brushing frequency. Children who regularly used supplements had higher TFI scores than those who did not. Children with a college-educated father had higher TFI scores than those whose fathers had less education., Conclusions: Higher fluoride exposure slightly increased the likelihood that a child had a higher TFI score, especially when more fluoridation technologies were used at home., (Copyright 2003 S. Karger AG, Basel)

Knowledge concerning risk factors for primary dentition caries in young children is incomplete. Models are presented for caries development using longitudinally gathered fluoride exposure and dietary intake data in the Iowa Fluoride Study. Primary tooth caries examinations were conducted at age 5. Dietary (beverage) and fluoride exposure data were gathered longitudinally from age 6 weeks through 4 years (n = 291); 23% had decayed or filled surfaces. Logistic regression revealed that beverage components and toothbrushing made unique contributions to caries experience. Water consumption (36-48 months), milk consumption (24-36 months), and fluoridated toothpaste brushings (36-48 months) were negatively associated with caries; sugared beverages and milk (6 weeks to 12 months) were positively associated. Although fluoride exposure is important, sugared beverages contribute substantially to caries risk, while water and milk consumption and frequent toothbrushing early can have protective effects., (Copyright 2003 S. Karger AG, Basel)

Objective: To compare permanent tooth surface-specific progression/reversal changes between fluoridation-ended (F-E) and still-fluoridated (S-F) communities in British Columbia, Canada, over a 3-year period., Methods: D1D2MFS examinations were contrasted for 2,964 schoolchildren in 1993/94 (grades 2, 3, 8 and 9) and 1996/97 (grades 5, 6, 11 and 12). Generalized Estimating Equation (GEE) models explored the relation between progression/reversal changes and fluoridation status, age, gender, socioeconomic status, and dietary/fluoride histories., Results: Within a scenario of low levels of caries overall, few children had multiple surfaces progressing. At least one smooth surface progressed in 31.4% of subjects; at least one pit-and-fissure (PF) surface progressed in 43.1% of subjects. At least one smooth surface reverted in 89% of subjects who had reversible stages; at least one PF surface reverted in 23.8% of subjects who had reversible stages. GEE (smooth) indicated that odds ratios of progression were twice as large in the F-E site compared to the S-F site, and slightly increased in older participants and in participants exposed to more fluoride technologies. GEE (PF) also indicated that progression was slightly more common in the F-E site; more frequent snacking and lower parental educational attainment had modest associations with increased progression in PF surfaces. For the two types of surfaces, GEE models demonstrated that unerupted surfaces were less likely to progress than sound surfaces. No associations were found between reversals and independent variables., Conclusion: Progressions were found to be weakly linked to socio-demographic factors; baseline surface statuses were better predictors of progression. Using the current definitions for disease transitions, F-E communities had more frequent progressions than a S-F community.

In recent studies of 'low natural killer (NK) cell syndrome', low NK activity was measured in individuals who were symptomatic, and therefore a causal relationship between low NK activity and infectious or other disease manifestations could not be concluded. However, preliminary work by members of our collaborative team (S.L. and R.H.) provided some indications for chronic low NK activity preceding and predicting subsequent infectious morbidity. This present study was designed to address this causal question in a larger sample, using a longitudinal design. Subjects were 106 healthy normal volunteers from the community. They were examined medically and psychosocially at baseline, and were then followed over a 6-month interval, with serial monthly assessments over the study period. The results supported our hypothesis that individuals who were currently healthy, but who exhibited a pattern of natural immunity characterized by persistently low NK cytotoxicity would be at risk for development of infectious sequelae over a 6-month follow-up period. The results also showed that younger age and the perception of more severe 'hassles' or stressors also predicted more infectious morbidity during the 6-month study period. Chronological age appeared to have both a direct, as well as indirect (via NK activity) association with illness outcome. Contrary to our expectation, the report of environmental stressors was directly associated with illness outcome, but not indirectly associated with outcome via natural immunity.

Previous work of ours has demonstrated that a significant amount of natural killer (NK) activity variance after surgery in stage I and II breast cancer patients could be accounted for by both the estrogen receptor (ER) status of the tumor and by social factors, namely, perceived social support and seeking social support as a general coping strategy. As considerable evidence has accumulated that social support in both animal and human populations may have survival value, we sought to test the reliability of this regression model, using coping and perceived support factor values obtained at 3 months after surgery to account for concurrent follow-up NK activity in this serially assessed group of patients. It was found that the most significant variable predicting NK activity at follow-up was tumor ER concentration, with higher NK activity associated with ER- status. In addition, seeking social support as a coping strategy, as well as the perceived quality of support, also entered the model to account for a significant amount of NK activity variance (multivariate F = 5.25, p less than 0.001). If, as the literature suggests, NK activity is relevant to breast cancer control, and since ER- tumors have a worse prognosis, we suggest here that perhaps such tumors are resistant to control by NK cells because they lack the ability to attract an accumulation of effector cells to the tumor site, or because blocking factors at the site of the tumor prevent local tumor control at the site of action. The finding related to social support also replicates results from an independent sample of breast cancer patients. This finding, taken together with other evidence that this social variable is associated with longer survival in breast cancer populations, underscores the potential importance of this social support variable. Our findings also suggest one possible immunological variable involved, with potential clinical significance, for this patient population.

This current study is concerned with the identification of the incidence of persistently low natural killer (NK) cell activity in an essentially healthy population of young adults, and the characterization of the psychological profile associated with this pattern of NK activity. Eighty-eight individuals, between the ages of 18 and 44 years, were accrued to this project. Subjects were tested serially, at baseline induction into the study, and at 2 and 4 weeks follow-up. Baseline assessment included a complete physical examination and laboratory work-up in order to exclude anyone ill at the time of enrollment, and to have complete physical status information on all subjects at the time of accrual. NK activity, urinary catecholamine levels and psychological status were also assessed at baseline, and at the specified follow-up intervals. Individuals with low NK activity were operationally defined as those having NK function either below the group mean, or below the group lowest quartile, at baseline and at two follow-up assessments. Results showed that in both univariate analyses, as well as in logistic regression models, age and the perception of environmental stressors or 'hassles' predicted persistently low NK activity. Younger subjects, who perceived environmental events to which they were exposed as more serious in nature, were more likely to exhibit a persistently low NK profile over time than older individuals who perceived daily events as less important to them.