IRE1 Less Common Homozygous Genotype in Families With Positive History of Cancer and Individuals Born With Cleft Lip/Palate.

ABSTRACT: The aim of this study was to test if the marker rs196929 in IRE1 associated with cleft lip and palate depending on the family history for cancer. A consecutive sample of 836 individuals were recruited between April and October of 2019 (303 born with cleft lip and palate, 256 relatives mostly of the maternal side of individuals born with cleft lip and palate, and 277 unaffected unrelated individuals). Parents or guardians of the children answered a questionnaire with basic demographic information about their children and their family history of cleft lip and palate and cancer. DNA was obtained from whole saliva and IRE1 rs196929 was genotyped using TaqMan chemistry and end-point analysis. Over-representation of alleles was determined using chi-square as implemented in PLINK using an alpha of 0.05. There was an excess of less common homozygotes of IRE1 rs196929 among relatives of individuals born with cleft lip and palate when they had positive family history of cancer in comparison with individuals born with cleft lip and palate or with unrelated unaffected individuals (P = 0.0006 and P < 0.001, respectively). This pattern was similar when families reported one type of cancer or multiple ones, or when cancer affecting females (breast or reproductive tract) or the structures of the gastro-intestinal tract were considered. These results provide support for a role of the ER stress IRE1-XPB1 pathway in the higher frequency of cancer in families of individuals born with cleft lip and palate.

Talon Cusp Associates With MMP2 in a Cohort of Individuals Born With Oral Clefts.

OBJECTIVE: The aim of this study was to use dental development as a tool to subphenotype oral clefts and investigate the association of MMP2 with dentin-pulp complex anomalies, in order to identify dental anomalies that are a part of a "cleft syndrome." DESIGN: Two hundred and ninety individuals born with cleft lip and palate were evaluated and several clinical features, such as cleft completeness or incompleteness, laterality, and presence of dental anomalies were used to assess each individual's cleft status. We tested for overrepresentation of MMP2 single nucleotide polymorphism rs9923304 alleles depending on individuals having certain dental anomalies. Chi-square and Fisher exact tests were used in all comparisons (α = .05). RESULTS: All individuals studied had at least one dental anomaly outside the cleft area. Significant differences between individuals born with clefts with and without talon cusp (P = .04) were observed for the frequency of the MMP2 less common allele. CONCLUSION: All individuals born with cleft lip and palate had alterations of the dentition, and a quarter to half of the individuals had alterations of the internal anatomy of their teeth, which further indicates that dental anomalies can be considered as an extended phenotype for clefts. MMP2 was associated with talon cusp in individuals born with oral clefts.

IRF6, MSX1, TGFA, dental anomalies, and skeletal malocclusion.

OBJECTIVE: Verify the presence of association between four variables-transforming growth factor α (TGFA; C/T rs1523305), interferon regulatory factor 6 (IRF6; A/C rs2013162), muscle segment homeobox 1 (MSX1; A/G rs12532), and dental anomalies-with skeletal malocclusion by comparing these four variables with Angle Classes I, II, and III, and normal, hyperdivergent, and hypodivergent growth patterns. METHODS: A total of 505 orthodontic records of patients older than 8 years were evaluated. The sample consisted of 285 (56.4 per cent) females, 220 (43.6 per cent) males, 304 (60.2 per cent) Whites (the rest were mixed Blacks with Whites), with a mean age of 20.28 (±10.35) years (ranging from 8 to 25 years). Eight cephalometric points, which served as the anatomical framework for obtaining angles and cephalometric measurements, were used for skeletal characterization using the Dolphin Software. Samples of saliva were collected and the DNA was extracted, diluted and quantified. Markers in TGFA, IRF6, and MSX1 were used and genotypes were obtained using TaqMan chemistry. Odds ratio (OR) and 95 per cent confidence interval (CI) calculations, chi-square, Fisher's Exact, Mann-Whitney, and correlation coefficient tests (significance level: 95 per cent) were performed. Bonferroni correction was applied and an alpha of 0.0006 was considered statistically significant. RESULTS: There was no statistically significant associations between markers in TGFA or IRF6 with skeletal malocclusions. Tooth agenesis was associated with facial convexity (P < 0.001). MSX1 was associated with Class II skeletal malocclusion (P = 0.0001, OR = 0.6, CI = 0.46-0.78). CONCLUSION: Individuals with tooth agenesis were more likely to have a convex face. MSX1 was associated with Class II skeletal malocclusion.

Fine-Mapping of Xq25.1-27.2 Shows Association of Early Childhood Caries with Genetic Variants Depending on Dietary Habits, Protecting Children Who Drink Milk before Going to Bed.

Early childhood caries (ECC) is a chronic, infectious disease that affects the primary dentition of young children. It is the result of unequal contributions of risk factors and protective factors that influence the disease. The aim of this study was to assess if the X chromosome region previously linked to caries was associated with ECC. Two hundred and fifty-nine unrelated children with no chronic illnesses from 2 to 5 years of age who had no systemic fluoride consumption 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 ten genes were studied. Genotyping of the selected polymorphisms was carried out by real-time polymerase chain reaction. Regression analyses were performed comparing individuals with and without caries experience. Of 259 subjects, 123 were caries free. The markers in Xq25.1-27.2 were associated with ECC when children were using milk bottle for longer times (p = 0.01) and had more snacks over the course of a day (p = 0.05). Conversely, the markers in the X chromosome studied here were protective for ECC (p = 0.008) in children consuming milk before going to sleep. The genes located in the X chromosome possibly contribute to ECC and have an impact on ECC depending on the dietary habits.

Complex patterns of response to oral hygiene instructions: longitudinal evaluation of periodontal patients.

BACKGROUND: Oral hygiene instruction is an intervention widely practiced but increased knowledge about oral health does not necessarily dramatically impact oral disease prevalence in populations. We aimed to measure plaque and bleeding in periodontal patients over time to determine patterns of patient response to oral hygiene instructions. METHODS: Longitudinal plaque and bleeding index data were evaluated in 227 periodontal patients to determine the impact of oral hygiene instructions. Over multiple visits, we determined relative plaque accumulation and gingival bleeding for each patient. Subsequently, we grouped them in three types of oral hygiene status in response to initial instructions, using the longitudinal data over the period they were treated and followed for their periodontal needs. These patterns of oral hygiene based on the plaque and gingival bleeding indexes were evaluated based on age, sex, ethnic background, interleukin 1 alpha and beta genotypes, diabetes status, smoking habits, and other concomitant diseases. Chi-square and Fisher's exact tests were used to determine if any differences between these variables were statistically significant with alpha set at 0.05. RESULTS: Three patterns in response to oral hygiene instructions emerged. Plaque and gingival bleeding indexes improved, worsened, or fluctuated over time in the periodontal patients studied. Out of all the confounders considered, only ethnic background showed statistically significant differences. White individuals more often than other ethnic groups fluctuated in regards to oral hygiene quality after instructions. CONCLUSIONS: There are different responses to professional oral hygiene instructions. These responses may be related to ethnicity.

Caries: review of human genetics research.

The NIH Consensus Development Program released a statement in 2001 (http://consensus.nih.gov/2001/2001DentalCaries115html.htm) and listed six major clinical caries research directions. One of these directions was the need for genetic studies to identify genes and genetic markers of diagnostic, prognostic and therapeutic value. This last decade has seen a steep increase in studies investigating the presence of genetic factors influencing individual susceptibility to caries. This review revisits recent caries human genetic studies and provides a perspective for future studies in order to fulfil their promise of revolutionizing our understanding of and the standard of care for the most prevalent bacteria-mediated non-contagious disease in the world.

Prevalence of oral trauma in Para-Pan American Games athletes.

The aim of this cross-sectional epidemiological survey was to assess the prevalence of oral trauma in athletes representing 25 countries competing at the most recent Para-Pan American Games (III PARAPAN) held in Rio de Janeiro, Brazil. The study was approved by the appropriate institutional review board. The examiners participated in standardization and calibration training sessions before the field phase began. Invitations were sent to >1200 participating athletes competing in eight sports and to the Medical Committee of the Para-Pan American Sports Organization before and during the III PARAPAN. A convenience sample of 120 athletes was recruited. After signing an informed consent, all athletes answered a questionnaire. Data were collected at the clinical examination and recorded in a specific trauma form. The mean age of the athletes was 32.5 years. Males comprised 79.2% of the sample; females 20.8%. The prevalence of oral trauma among the athletes was 47.5% (N = 57). However, only 15 athletes reported that these traumatic injuries were sports-related. The sport with the highest prevalence of oral trauma was judo (75%); the least was volleyball with no reported traumatic injuries. The most common traumatic injury was enamel fracture (27.4%). The teeth most affected were the maxillary permanent central incisors (N = 19), followed by the maxillary premolars (N = 8). On the basis of the results of this study of oral trauma among athletes examined at the III PARAPAN, a recommendation for enhanced educational efforts and the use of properly fitted mouthguards to prevent traumatic injuries among high-performance athletes with disabilities seems warranted.

The effect of 1% chlorhexidine varnish and 40% xylitol solution on Streptococcus mutans and plaque accumulation in children.

PURPOSE: The purpose of this study was to determine the effect of the association of 1% chlorhexidine varnish (CHX) and 40% xylitol solution (XYL) on Streptococcus mutans (SM) counts and plaque indices in 2- to 5-year-olds. METHODS: Sixty-eight children were selected with medium levels (1 x 10³) to very high levels (>1 x 105) of SM in the saliva. Subjects were divided into 4 groups of 17 children each: (1) CHX; (2) CHX+XYL; (3) XYL; and(4) 0.05% sodium fluoride (F). An assessment of SM levels and plaque indices was done on all children at baseline, 15 days, and at 1, 3, and 6 months. SM levels were determined by the spatula method. RESULTS: Although the reduction in SM counts in all groups was statistically significant, differences among groups were not observed, and the CHX and F groups seemed to show the greatest effect. Plaque reduction was observed in all groups, whereas statistically significant decreases among groups were not observed. CONCLUSIONS: One percent chlorhexidine varnish associated with 40% xylitol solution tested in the present study does not provide significant suppression of Streptococcus mutans counts and reduction of plaque accumulation at any follow-up time points.

Gene-environment interaction in molar-incisor hypomineralization.

Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH's development, but no conclusive risk factors have shown the source of the disease. During head and neck development, the interferon regulatory factor 6 (IRF6) gene is involved in the structure formation of the oral and maxillofacial regions, and the transforming growth factor alpha (TGFA) is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis. In this present study, it was hypothesized that these genes interact and contribute to predisposition of MIH. Environmental factors affecting children that were 3 years of age or older were also hypothesized to play a role in the disease etiology. Those factors included respiratory issues, malnutrition, food intolerance, infection of any sort and medication intake. A total of 1,065 salivary samples from four different cohorts were obtained, and DNA was extracted from each sample and genotyped for nine different single nucleotide polymorphisms. Association tests and logistic regression implemented in PLINK were used for analyses. A potential interaction between TGFA rs930655 with all markers tested in the cohort from Turkey was identified. These interactions were not identified in the remaining cohorts. Associations (p<0.05) between the use of medication after three years of age and MIH were also found, suggesting that conditions acquired at the age children start to socialize might contribute to the development of MIH.

Prevalence of dental trauma in Pan American games athletes.

The aim of this cross-sectional epidemiological survey was to assess the prevalence of dental trauma in athletes representing 42 countries competing at the most recent Pan American Games (XV Pan Am) held in Rio de Janeiro, Brazil in July of 2007, and to determine prior use and type of mouthguard among this group of athletes. The examiners participated in standardization and calibration training sessions before the field phase began. Invitations were sent to >5500 participating athletes competing in 41 sports and to the Medical Committee of the Pan American Sports Organization before and during the XV PAN. A convenience sample of 409 athletes was recruited. After signing an informed consent, all athletes answered a questionnaire. Data were collected at the clinical examination and recorded on a specific trauma form. The mean age of the athletes was 24.4 +/- 5.3 years. Males comprised 55% of the sample; females 45%. The prevalence of dental trauma among the athletes was 49.6% (n = 203) with no gender-based differences. Most of these injuries (63.6%) were related to activities during training or competition. Sports with the highest injury prevalence were wrestling (83.3%), boxing (73.7%), basketball (70.6%) and karate (60%). The most common injury was enamel fracture (39.8%); root fracture was the least common (0.4%). The teeth most affected were the maxillary permanent central incisors (n = 113), followed by the mandibular central incisors (n = 19). Based on the results of this study, nearly one-half of the subjects had experienced previous dental trauma; the majority related to sports activities. Furthermore, only 17% of the athletes reported prior mouthguard use; the most frequent mouthguards reported were boil-and-bite. These results suggest the importance of enhanced educational efforts and the use of properly fitted mouthguards to reduce dental trauma among athletes in international sports competition, especially in sports where mouthguards are not mandatory.

Biomarkers for Lifetime Caries-Free Status.

The purpose of this study was to address the hypothesis that extreme outcomes of dental caries, such as edentulism or prematurely losing permanent teeth are associated with genetic variation in enamel-formation genes. After scanning 6206 individuals, samples of 330 were selected for this study. Tested phenotypes included patients who were edentulous by age 30, patients with missing first molars by age 30, patients with missing second molars by age 30, and caries-free patients. Fourteen single nucleotide polymorphisms were genotyped by TaqMan chemistry. The analyses of each phenotype were performed using the software PLINK with an alpha of 0.05. Nominal associations were found between rs12640848 in enamelin (p = 0.05), rs1784418 in matrix metallopeptidase 20 (p = 0.02), and rs5997096 in the tuftelin interacting protein 11 and being caries-free at the age of 60. When combining patients that were missing both first mandibular molars and missing both second mandibular molars, no associations were found. Matrix metallopeptidase 20, and tuftelin interacting protein 11 also showed trends for association with being caries-free. Genetic variation in TFIP11, MMP20, and ENAM may have a protective effect increasing the chances of individuals preserving their teeth caries-free over a lifetime.

A Snapshot of the Prevalence of Molar Incisor Hypomineralization and Fluorosis in Pittsburgh, Pennsylvania, USA.

Purpose: The prevalence of molar incisor hypomineralization in the United States is unknown. The condition is defined via the presence of demarcated opacities of varying color, porous enamel, advanced susceptibility or progression of dental caries, and sensitivity. The purpose of this study was to establish the prevalence of molar incisor hypomineralization (MIH) in Pittsburgh, Pa., USA. Methods: A total of 104 patients (64 females and 40 males ranging in age from seven to 32 years) from the University of Pittsburgh were screened for the clinical signs of MIH between May 15 and July 31, 2019. MIH was defined according to international guidelines. Results: A total of 9.6 percent of patients screened presented with the clinical signs of MIH; 15.4 percent of patients screened presented with clinical signs aligning with dental fluorosis. Conclusions: Molar incisor hypomineralization is prevalent and clinically relevant in Pittsburgh. American clinicians should start recording the diagnoses of MIH to facilitate establishing national prevalence data and increase knowledge and treatment.

Maxillary incisor enamel defects in individuals born with cleft lip/palate.

Cleft lip with or without cleft palate (CLP) is considered the most frequent congenital malformations of the head and neck, with cleft individuals exhibiting more chances of presenting abnormalities such as developmental defects of enamel (DDE). Matrix metallopeptidase 2 (MMP2) is a membrane-bound protein with collagen-degrading ability and has important roles in tooth formation and mineralization. The aim of this study was to evaluate the frequency, location, severity and extent of DDE found in the maxillary incisors for groups of individuals born with CLP, as well as understanding their relationship with the cleft side. Besides, this study addresses the hypothesis that DDE can be influenced by variation in the MMP2 genes (rs9923304). Individual samples, clinical history, intraoral photographs and panoramic radiographs were obtained from 233 patients under treatment at the Cleft Lip and Palate Service of the University Hospital Lauro Wanderley at the Federal University of Paraíba. Digital images were examined by the same evaluator using the Classification of Defects According to the Modified DDE Index, and then loaded into the Image Tool software, where two measurements were made: total area of the buccal surface (SA) and the area of the DDE (DA), obtaining the percentage of the surface area affected (%SAD) (ICC = 0.99). Genomic DNA was extracted from saliva samples from 124 participants. Genotyping was carried out using TaqMan chemistry for one marker in MMP2 (rs9923304). Statistical analyses were performed by The Jamovi Project software. The Shapiro-Wilk test was applied, followed by the Student's t-test and the Mann-Whitney test. Chi-square and Fisher's exact tests, and odds ratio (OR) with 95% confidence interval (CI) calculations were used to determine Hardy-Weinberg equilibrium and statistically significant differences with an alpha of 0.05. No significant differences in the prevalence and extent of enamel defects were found between male and female individuals born with CLP (p = 0.058256). The frequency of individuals presenting teeth with DDE, in relation to the cleft and non-cleft side, was statistically different (p <0.001; OR = 7.15, CI: 4.674> 7.151> 10.942). However, the averages of %SAD were similar (p = 0.18). The highest means of the %SAD were found in individuals with bilateral cleft lip with or without cleft palate (BCLP) when compared to individuals with unilateral cleft lip with or without cleft palate (UCLP), for the teeth inside (IA) and outside the cleft area (OA) (p <0.001). Regardless of the cleft side, individuals with BCLP were 7.85 times more likely to have more than one third of the tooth surface affected, showing more frequently defects in the three thirds (OA: p <0.001) (IA: p = 0.03), as well as a higher frequency of more than one type of defect (OA: p = 0.000358) (IA: p = 0.008016), whereas in UCLP, defects were isolated and restricted to only one third, more frequently, the incisal third (OA: p = 0.009) (IA: p = 0.001), with greater frequency of milder defects, such as demarcated (p = 0.02) and diffuse (p = 0.008) opacities. A higher frequency of the T allele, less common, was observed in the group of CLP individuals who had all the affected teeth or at least two teeth with %SAD greater than 20% (p = 0.019843). Our results suggest that MMP2 may have a role in the cases that presented DDE and genotyping rs9923304 could serve as the basis for a genomic approach to define risks for individuals born with CLP. Frequency and severity of DDE is strongly related to the CLP phenotype, since the highest values were found for BCLP. However, the extent of the DDE is independent of its relationship with the side of the cleft.

Aquaporin locus (12q13.12) might contribute to susceptibility of temporomandibular joint disorder associated with periodontitis.

Aquaporins (AQPs) are membrane channels that provide for transport of water and other small molecules across the lipid bilayer of cells. Their function is essential for physiologic processes such as cell volume regulation, chondrocyte hypertrophy during appendicular skeletal growth, water reabsorption in the kidney tubules, and water excretion by the salivary glands. The ten AQP isoforms show tissue specificity and are involved in different pathologies and inflammatory diseases. This study addresses the hypothesis that arthritis, periodontitis, and temporomandibular joint disorders (TMDs) can be influenced by variation in the AQP genes at 12q13.12 locus. Salivary samples of 688 individuals were obtained from the Dental Registry and DNA Repository project at the University of Pittsburgh. Ten polymorphisms in four AQP genes (AQP1, 2, 5, and 6) were genotyped and correlated to disease status as reported by patients. Associations were found between the single nucleotide polymorphism (SNP) rs467323 in AQP2 and TMD in both genotypic (p = 0.03) and recessive (p = 0.02) models, and between rs1996315 in AQP6 and periodontitis (p = 0.05). Combined analysis of TMD and periodontitis showed an association with rs3741559 in AQP2 (p = 0.02). When conducting haplotype analysis of rs467323 and rs10875989 in AQP2, the haplotype CT showed an association with the TMD phenotype (p = 0.007). Our results suggest that the aquaporin locus at 12q13.12 may contribute to the pathogenesis of inflammatory conditions such as periodontitis and TMD. Thus, oral and skeletal health are correlated and potential susceptibility screening strategies may be developed.

Phenome-Wide Scan Finds Potential Orofacial Risk Markers for Cancer.

Cancer is a disease caused by a process that drives the transformation of normal cells into malignant cells. The late diagnosis of cancer has a negative impact on the health care system due to high treatment cost and decreased chances of favorable prognosis. Here, we aimed to identify orofacial conditions that can serve as potential risk markers for cancers by performing a phenome-wide scan (PheWAS). From a pool of 6,100 individuals, both genetic and epidemiological data of 1,671 individuals were selected: 350 because they were previously diagnosed with cancer and 1,321 to match to those individuals that had cancer, based on age, sex, and ethnicity serving as a comparison group. Results of this study showed that when analyzing the individuals affected by cancer separately, tooth loss/edentulism is associated with SNPs in AXIN2 (rs11867417 p = 0.02 and rs2240308 p = 0.02), and leukoplakia of oral mucosa is associated with both AXIN2 (rs2240308 p = 0.03) and RHEB (rs2374261 p = 0.03). These phenotypes did not show the same trends in patients that were not diagnosed with cancer, allowing for the conclusion that these phenotypes are unique to cases with higher cancer risk.

Measuring the Microscopic Structures of Human Dental Enamel Can Predict Caries Experience.

OBJECTIVES: The hierarchical structure of enamel gives insight on the properties of enamel and can influence its strength and ultimately caries experience. Currently, past caries experience is quantified using the decayed, missing, filled teeth/decayed, missing, filled surface (DMFT/DMFS for permanent teeth; dmft/dmfs for primary teeth), or international caries detection and assessment system (ICDAS) scores. By analyzing the structure of enamel, a new measurement can be utilized clinically to predict susceptibility to future caries experience based on a patient's individual's biomarkers. The purpose of this study was to test the hypothesis that number of prisms by square millimeter in enamel and average gap distance between prisms and interprismatic areas, influence caries experience through genetic variation of the genes involved in enamel formation. MATERIALS AND METHODS: Scanning electron microscopy (SEM) images of enamel from primary teeth were used to measure (i) number of prisms by square millimeter and interprismatic spaces, (ii) prism density, and (iii) gap distances between prisms in the enamel samples. The measurements were tested to explore a genetic association with variants of selected genes and correlations with caries experience based on the individual's DMFT+ dmft score and enamel microhardness at baseline, after an artificial lesion was created and after the artificial lesion was treated with fluoride. RESULTS: Associations were found between variants of genes including ameloblastin, amelogenin, enamelin, tuftelin, tuftelin interactive protein 11, beta defensin 1, matrix metallopeptidase 20 and enamel structure variables measured (number of prisms by square millimeter in enamel and average gap distance between prisms and interprismatic areas). Significant correlations were found between caries experience and microhardness and enamel structure. Negative correlations were found between number of prisms by square millimeter and high caries experience (r value= -0.71), gap distance between prisms and the enamel microhardness after an artificial lesion was created (r value= -0.70), and gap distance between prisms and the enamel microhardness after an artificial lesion was created and then treated with fluoride (r value= -0.81). There was a positive correlation between number of prisms by square millimeter and prism density of the enamel (r value = 0.82). CONCLUSIONS: Our data support that genetic variation may impact enamel formation, and therefore influence susceptibility to dental caries and future caries experience. CLINICAL RELEVANCE: The evaluation of enamel structure that may impact caries experience allows for hypothesizing that the identification of individuals at higher risk for dental caries and implementation of personalized preventative treatments may one day become a reality.

Bruxism Throughout the Lifespan and Variants in MMP2, MMP9 and COMT.

Bruxism is a masticatory muscle activity characterized by grinding of the teeth and clenching of the jaw that causes tooth wear and breakage, temporomandibular joint disorders, muscle pain, and headache. Bruxism occurs in both adults and children. Clinical characteristics and habits were evaluated in an adult sample. Moreover, we used DNA samples from 349 adults and 151 children to determine the presence of association with specific genes. Genomic DNA was obtained from saliva. The markers rs2241145 and rs243832 (metalloproteinase 2 (MMP2)), rs13925 and rs2236416 (metalloproteinase 9 (MMP9)), and rs6269 (cathecol-o-methyltransferase (COMT)) were genotyped. Data were submitted to statistical analysis with a significance level of 0.05. In adults, in univariate logistic regression, presence of caries, attrition, and use of alcohol were increased in bruxism individuals (p < 0.05). In addition, in adults, there was an association between bruxism and MMP9 (rs13925, p = 0.0001) and bruxism and COMT (rs6269, p = 0.003). In children, a borderline association was observed for MMP9 (rs2236416, p = 0.08). When we performed multivariate logistic regression analyses in adults, the same clinical characteristics remained associated with bruxism, and orthodontic treatment was also associated, besides rs13925, in the AG genotype (p = 0.015, ORa: 3.40 (1.27-9.07)). For the first time, we provide statistical evidence that these genes are associate with bruxism.

Transforming growth factor-alfa gene (TGFA), human tooth agenesis, and evidence of segmental uniparental isodisomy.

We have previously reported an association between variants in the transforming growth factor-alfa gene (TGFA) and human tooth agenesis. To demonstrate in greater detail that TGFA contributes to tooth agenesis, we investigated additional markers in the gene. Cheek swab samples were obtained for DNA analysis from 116 patient/parent trios. Probands had at least one developmentally missing tooth, excluding third molars. Genotyping was performed using TaqMan assays. Linkage disequilibrium analysis and test of the transmission distortion of the marker alleles were performed. We confirmed that TGFA variants and haplotypes are associated with tooth agenesis. Moreover, it appears that preferential premolar agenesis is associated with TGFA, and patients with a family history of tooth agenesis would have an associated haplotype. Finally, we excluded that a TGFA microdeletion could cause sporadic agenesis in a case of upper lateral incisors and lower second premolars and suggest this case may be consequence of a segmental uniparental isodisomy.

Defining subphenotypes for tooth agenesis: does side matter?

OBJECTIVES: The etiology of tooth agenesis is still poorly understood. The identification of sub-populations with specific types of hypodontia (subphenotypes) would allow testing the specific hypothesis that certain genetic factors contribute to the specific subphenotype. The aim of this work was assessing a large cohort to verify if preferential tooth agenesis subphenotypes could be identified. METHOD: Panoramic radiographs of 1052 cases were examined and 1034 were used in this study. The presence of tooth agenesis was assessed in the study population. RESULTS: The frequency of tooth agenesis in the studied population was 3.77%. While bilateral cases did not differ in the frequency of agenesis by arch (p = 0.8), unilateral cases presented more commonly agenesis on the mandibular arch (p = 0.03). This result was clearly driven by the frequency of second premolar agenesis, which was the most common absent tooth in the studied population. Unilateral lower second premolar agenesis was found more often than bilateral agenesis (p = 0.047). CONCLUSIONS: Our findings that unilateral lower second premolar agenesis is more common than bilateral agenesis, with a trend for unilateral agenesis being more common on the right side may suggest specific genetic factors may be differentially expressed depending on the side.

The concept of exposure when selecting comparison groups for determining individual susceptibility to addiction to cigarette smoking.

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.