Genome-wide association study identifies novel caries-associated loci showing sex-specificity-A study on the Northern Finland Birth Cohort 1966.

A genome-wide association study was performed in sex-stratified groups representing three different caries phenotypes among adults. The study sample consisted of 46-year-old participants of the Northern Finland Birth Cohort 1966 study (n = 1481). The phenotypes for analyses were the dentin caries phenotype (persons having at least one tooth with dentin caries lesion), and the enamel caries phenotype (those having teeth with more than 10 enamel caries lesions), while the control group had <10 enamel caries lesions and no teeth with dentin caries, respectively. A third phenotype dubbed the caries severity phenotype had a below-average number of teeth with initial lesions and at least one extensive dentin caries lesion; their controls had an above-average number of teeth with initial caries lesions and no teeth with extensive dentin caries lesions. All analyses were performed for the whole group and for sex-stratified subgroups. In females, loci in chromosomes 2, 5, and 15 showed a statistically significant association with caries severity. In males, there was a novel association between chromosome 5 and dentin caries. The results of this study may suggest a genetic background of caries among adults. In the future, the detection of genetic predisposing variants may allow the identification of patients at risk for caries, even in the absence of behavioral and environmental risk factors.

Prevalence of Erosive Tooth Wear and Associated Dietary Factors among a Group of Finnish Adolescents.

The aim of this study was to investigate the prevalence and severity of erosive tooth wear (ETW) among Finnish adolescents and to evaluate how frequency as well as amount of the use of erosive products is associated with ETW. The study population consisted of 328 voluntary, >15-year-old secondary school students (males 49.1%, females 50.9%) in three municipalities in Finland. Clinical examination to measure ETW (BEWE index) was carried out by trained and calibrated dentists. Piloted questionnaires included questions on consumption of drinks, fruits and berries, as well as tooth brushing frequency. Means and medians of frequencies and amounts of consumed erosive products were calculated and associations with ETW severity were analysed by logistic regression models. One-third (36.9%) of the participants were in need of at least preventive measures for ETW (BEWE sum score ≥3), but severe ETW (BEWE sum score >9) was rare (2.1%). Boys had severe ETW significantly more frequently than girls (p < 0.001). Habitual consumption of erosive drinks was common especially among boys compared to girls (p = 0.001). ETW was significantly associated with the amount of consumed erosive drinks, fruits, or berries. The prevalence of ETW among adolescences in Finland seems to be at the same level as in other Nordic and European countries. Consumption of erosive products is common and thus, the risk for tooth erosion is high, especially in boys. In addition to erosive drinks, also berries and fruits are associated with ETW and should be included in individual dietary counselling when early signs of ETW are clinically detected.

Multicenter study to develop and validate a risk assessment tool as part of composite scoring system for erosive tooth wear.

OBJECTIVES: (i) To develop, validate, and apply in practice a new risk assessment tool for erosive tooth wear (ETW) including a risk factors questionnaire and a saliva secretion evaluation, which combined with a clinical index, can be part of an ETW composite scoring system; (ii) to assess ETW lesions and current and past erosive challenges in younger age groups. METHODS: The Tooth Surface Loss/Erosion Working Group of the European Association of Dental Public Health consisted of an international panel of experts designed the survey component of the new tool (Erosive Wear Assessment of Risk-EWAR) and confirmed its construct and content validity. After receiving ethical approvals and informed consents, the EWAR tool (questionnaire + saliva secretion evaluation) was applied in a multicenter cross-sectional study with 207 participants aged 15-21 years old from four countries (Finland, Greece, Romania, the USA). BEWE score was used for the clinical assessment of ETW. RESULTS: A total of 58.5% of participants had ETW. 10.9% and 20.3% of participants had low secretion of stimulated (< 1 ml/min) and unstimulated saliva (< 0.25 ml/min), respectively. The following factors were bivariately significantly associated with ETW: energy drink consumption, low secretion of stimulated saliva, juices consumption, erosive drink consumption for quenching thirst between meals, erosive drink kept in the mouth, feeling pain/icing after consuming something acidic or cold, and co-existence of other type of tooth wear. In regression analysis, only energy drink consumption (OR = 3.5, 95% CI: 1.39, 8.9), low secretion of stimulated saliva (OR = 36.3, 95% CI: 4.71, 78.94), and feeling pain/icing (OR = 8.8, 95% CI: 1.92, 40.04) remained significant. CONCLUSIONS: The examiners of the study reported that the EWAR tool appeared to be an affordable and easy-to-use instrument. Some challenges occurred during the saliva collection process. Inferential analysis revealed that the risk factors/indicators of low stimulated salivary flow, energy drink consumption, and pain/icing with ETW were considered the most important in ETW occurrence. CLINICAL RELEVANCE: EWAR tool combined with the BEWE clinical index can be used for ETW risk assessment for epidemiological studies and chairside use.

Knowledge on and treatment practices of erosive tooth wear among Finnish dentists.

OBJECTIVES: To investigate Finnish dentists' knowledge on and means of recording, detecting and diagnosing erosive tooth wear (ETW). Treatment options and possible differences in treatment decisions between general and specialized dentists were also evaluated. MATERIALS AND METHODS: An electronic questionnaire was sent by e-mail to 3664 Finnish dentists. Respondents' gender, age, work experience, field of specialty, and practice location were requested. The questionnaire also included a patient case where the dentists were asked about their choice of treatment. Statistical analyses were performed using means, proportions, and cross tabulations. RESULTS: Response rate was 24% (n = 866). Almost all respondents (98.0%) recorded ETW in patient files, but only 4.1% used a detailed scoring system. Of the respondents, 64.4% usually found the cause of ETW. Use of carbonated beverages (84.3%), energy drinks (57.0%), and reflux disease (53.1%) were reported to be probable causes. The majority of the respondents (80.9%) usually assessed patient's dietary history while 1.9% evaluated saliva secretion rate. When asked about treatment decisions of ETW patients, the differences between general dentists and specialized dentists were not as obvious as hypothesized. CONCLUSIONS: This study suggests that the Finnish dentists who participated in this survey are able to detect and/or diagnose erosive tooth wear, but there is variation in recording it. The differences in treatment decisions between general dentists and specialized dentists seem to be moderate. The treatment practices for ETW are not established and further research to create clinical guidelines seems to be needed.

Genome-Wide Association Study of Erosive Tooth Wear in a Finnish Cohort.

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.

Influence of Intrinsic Factors on Erosive Tooth Wear in a Large-Scale Epidemiological Study.

OBJECTIVE: To assess the influence of self-reported intrinsic factors [gastroesophageal reflux disease (GERD), long-term alcoholism, long-term heavy use of alcohol and multiple pregnancies] on erosive tooth wear in a middle-aged cohort sample. MATERIALS AND METHODS: Of the total Northern Finland Birth Cohort (NFBC 1966), a convenience sample (n = 3,181) was invited for an oral health examination in 2012-2013, of which 1,962 participated, comprising the final study group. Erosive tooth wear was assessed by sextants using the Basic Erosive Wear Examination Index (BEWE, 0-18). Clinical data were supplemented by questionnaires conducted in 1997/1998 and 2012/2013. The participants were divided into severe (BEWE sum ≥9) and no-to-moderate (BEWE sum 0-8) erosive wear groups, and the logistic regression model was applied. RESULTS: Selected intrinsic factors were quite rare in this cohort sample and explained only 5.9% of the difference in the prevalence and severity of erosive wear. Daily symptoms of GERD [odds ratio (OR) 3.8, confidence interval (CI) 1.2-12.0] and hyposalivation (OR 3.8, CI 1.2-11.8) were the strongest risk indicators for severe erosive wear. Additionally, variables associated with an elevated risk for severe erosive wear were diagnosed alcoholism at any point (OR 2.5, CI 0.7-9.7) and self-reported heavy use of alcohol in both questionnaires (OR 2.0, CI 0.6-6.2). Even low-dose long-term consumption of alcohol was associated with erosive wear. CONCLUSIONS: In this cohort sample, intrinsic factors such as GERD or alcoholism alone are relatively uncommon causes of erosive tooth wear. The role of long-term use of alcohol in the erosion process may be bigger than presumed.

Association of erosive tooth wear and dental caries in Northern Finland Birth Cohort 1966 - an epidemiological cross-sectional study.

BACKGROUND: The main aim of this cross-sectional study was to investigate the prevalence and severity of erosive tooth wear and its association with dental caries and socio-demographic factors among middle-aged Finnish adults. METHODS: Of the total Northern Finland Birth Cohort 1966 (n = 12,058), a convenience sample (n = 3181 adults) was invited for an oral health examination of which 1962 (61.7 %) participated, comprising the final study group. Clinical examinations were carried out by trained and calibrated dentists. Erosive tooth wear was assessed by sextants using the Basic Erosive Wear Examination Index (BEWE, 0-18) and dental caries at surface level using the ICDAS criteria (0-6). Socio-demographic data were obtained from a postal questionnaire. A logistic regression model was generated to test the association of the variables. RESULTS: The prevalence of erosive tooth wear was 75 % and the mean of the BEWE sum score was 3.4 (SD 3.30). Almost half of the members needed non-invasive or invasive measures to prevent further progression of the condition. Of those with erosive lesions, 14.6 % suffered from severe erosive tooth wear. There was a strong positive relationship between the presence of severe erosive tooth wear (BEWE sum score ≥9) and male gender and restorative treatment need. CONCLUSIONS: Erosive tooth wear is a common finding in Finnish adult population; almost one in ten suffer from severe erosive tooth wear. Restorative treatment need seems to be associated with severe erosive tooth wear.

Different Risk Factors for Erosive Tooth Wear in Rural and Urban Nepal: A National Study.

BACKGROUND: Erosive tooth wear (ETW) is of growing concern, but data on ETW among Nepalese children are scarce. The main aim of the study was to investigate the prevalence and severity of ETW among Nepalese schoolchildren. We also aimed to analyse the risk indicators for ETW according to location (rural/urban) and the role of obesity in the risk for ETW. METHODS: This national study was conducted among 5-15-year-old Nepalese schoolchildren from different regions. Altogether, 1137 out of 1151 schoolchildren participated in both a clinical examination and a survey. ETW was recorded using the Basic Erosive Wear Examination. RESULTS: The prevalence of ETW was 65%. One-fifth of the examined subjects were in need of preventive or restorative treatment. Living in an urban area and studying in a private school were protective factors for ETW, whereas consuming fruits frequently and using charcoal for tooth cleaning increased the odds for ETW. Central obesity was the strongest risk indicator for ETW among urban residents. CONCLUSIONS: ETW of low severity is common among Nepalese children and adolescents. Socio-demographic factors influence the prevalence of ETW in Nepal and there seems to be different factors that play a role in the ETW process according to location of residence.

Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.

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.

TUFT1, a novel candidate gene for metatarsophalangeal osteoarthritis, plays a role in chondrogenesis on a calcium-related pathway.

Osteoarthritis (OA) is the most common degenerative joint disorder and genetic factors have been shown to have a significant role in its etiology. The first metatarsophalangeal joint (MTP I) is highly susceptible to development of OA due to repetitive mechanical stress during walking. We used whole exome sequencing to study genetic defect(s) predisposing to familial early-onset bilateral MTP I OA inherited in an autosomal dominant manner. A nonsynonymous single nucleotide variant rs41310883 (c.524C>T, p.Thr175Met) in TUFT1 gene was found to co-segregate perfectly with MTP I OA. The role of TUFT1 and the relevance of the identified variant in pathogenesis of MTP I OA were further assessed using functional in vitro analyses. The variant reduced TUFT1 mRNA and tuftelin protein expression in HEK293 cells. ATDC5 cells overexpressing wild type (wt) or mutant TUFT1 were cultured in calcifying conditions and chondrogenic differentiation was found to be inhibited in both cell populations, as indicated by decreased marker gene expression when compared with the empty vector control cells. Also, the formation of cartilage nodules was diminished in both TUFT1 overexpressing ATDC5 cell populations. At the end of the culturing period the calcium content of the extracellular matrix was significantly increased in cells overexpressing mutant TUFT1 compared to cells overexpressing wt TUFT1 and control cells, while the proteoglycan content was reduced. These data imply that overexpression of TUFT1 in ATDC5 inhibits chondrogenic differentiation, and the identified variant may contribute to the pathogenesis of OA by increasing calcification and reducing amount of proteoglycans in the articular cartilage extracellular matrix thus making cartilage susceptible for degeneration and osteophyte formation.

Is a Basic Erosive Wear Examination (BEWE) reliable for recording erosive tooth wear on 3D models?

OBJECTIVES: To assess the reliability of the BEWE index on 3D models and to compare 3D-assessed erosive tooth wear scores with clinically detected scores. METHODS: In total, 1964 members of the Northern Finland Birth Cohort 1966 participated in a standardized clinical dental examination including the Basic Erosive Wear Examination (BEWE) and dental 3D modelling at the age of 45-46 years. Of those examined, 586 were randomly selected for this study. 3D models were assessed using the same BEWE criteria as in the clinical examination. Calculated kappa values as well as the prevalence and severity of erosive wear according to the clinical examination and 3D models were compared. Re-examinations were performed to calculate intra- and inter-method and -examiner agreements. RESULTS: The BEWE index on 3D models was reproducible; the mean intra- and inter-examiner agreement were 0.89 and 0.87, respectively, for sextant level, and 0.64 and 1, respectively, for BEWE sum scores. Erosive tooth wear was recorded as more severe in 3D models than in the clinical examination, and inter-method agreement was 0.41 for severe erosive wear (BEWE sum>8). The biggest inter-method differences were found in upper posterior sextants. CONCLUSIONS: The BEWE index is reliable for recording erosive tooth wear on 3D models. 3D models seem to be especially sensitive in detecting initial erosive wear. Additionally, it seems that erosive wear may be underscored in the upper posterior sextants when assessed clinically. Due to the nature of 3D models, the assessment of erosive wear clinically and on 3D models may not be entirely comparable. CLINICAL SIGNIFICANCE: 3D models can serve as an additional tool to detect and document erosive wear, especially during the early stages of the condition and in assessing the progression of wear. When scoring erosive wear clinically, care must be taken especially when assessing upper posterior sextants.