Calcification patterns and morphology of Sella turcica are related to anteroposterior skeletal malocclusions: A cross-sectional study.

BACKGROUND: The sphenoid bone is an irregular, unpaired, symmetrical bone located in the middle of the anterior skull and is involved in craniofacial growth and development. Since the morphology of Sella turcica (ST) is associated with different craniofacial patterns, this study aimed to investigate if there is a correlation between ST morphology on the one hand and sagittal craniofacial patterns on the other hand. METHODS: This study was conducted with a convenience sample that included Brazilian individuals undergoing orthodontic treatment. Lateral cephalograms were used to evaluate the calcification pattern and morphology of ST, as well as skeletal class by analyzing the ANB angle. Pearson's chi-square test with Bonferroni post-hoc test was performed to evaluate the association between ST calcification pattern and morphology, and anteroposterior skeletal malocclusion. The established significance level was 0.05. RESULTS: The study collective was comprised of 305 orthodontic patients (178 (58.4 %) female, 127 (41.6 %) male), who had a mean age of 23.2 (±10.6) years. 131 participants (42.9 %) presented skeletal class I, 142 (46.6%) skeletal Class II, and 32 (10.5%) had a skeletal class III. The degree of prognathism of the mandible showed a homogenous distribution within the study collective (91 (29.9 %) orthognathic, 100 (32.9 %) retrognathic, 113 (37.2 %) prognathic mandible). Concerning the maxilla, 92 (30.2%) individuals presented an orthognathic upper jaw, whereas 60 (19.7%) showed maxillary retrognathism and 153 (50.2%) maxillary prognathism. Compared to patients with skeletal class I, skeletal class III individuals presented significantly more hypertrophic posterior clinoid process (p<0.007) and pyramidal shape of the dorsum of the ST (p<0.038). CONCLUSIONS: Our results suggest that the hypertrophic posterior clinoid process and pyramidal shape of the ST dorsum are more prevalent in individuals with skeletal class III malocclusion.

Investigating the association between dental age and polymorphisms in genes encoding estrogen receptors.

BACKGROUND: Genetic polymorphisms have been shown to influence several physiological traits, including dental and craniofacial characteristics. Understanding the clinical relevance of genetic polymorphisms in dental practice is crucial to personalize treatment plans and improve treatment outcomes. OBJECTIVE: to evaluate the association between dental age and genetic polymorphisms in genes encoding estrogen receptors alpha and beta (ESR1 and ESR2, respectively) in a sample of Brazilian children. METHODOLOGY: This retrospective cross-sectional study was performed with children undergoing orthodontic treatment. Patients with syndromes, congenital anomalies, craniofacial deformities, under hormonal or systemic treatment, and with a previous history of facial trauma were excluded. Panoramic radiographs were used to assess dental age according to the Demirjian, Goldstein, and Tanner method. A delta [dental age-chronological age (DA-CA)] was obtained, which shows whether the patient tends to have a normal, delayed (negative values), or advanced (positive values) dental age. DNA isolated from buccal cells was used to genotype four genetic polymorphisms: rs9340799 (A>G) and rs2234693 (C>T), located in ESR1; and rs1256049 (C>T) and rs4986938 (C>T), located in ESR2. A statistical analysis was performed and values of p<0.05 indicated statistical difference. RESULTS: A total of 79 patients were included, 44 (55.70%) girls and 35 (44.30%) boys. The Demirjian, Goldstein, and Tanner method, in general, overestimated patients' age by 0.75 years. There was no difference in the delta of dental age between the sexes (p>0.05). Genetic polymorphisms in ESR1 and ESR2 were not associated with dental age (p>0.05). CONCLUSION: The studied genetic polymorphisms in ESR1 and ESR2 were not associated with dental age in Brazilian children.

Testosterone suppression impacts craniofacial growth structures during puberty : An animal study.

AIM: Hormones play a crucial role in growth development; however, the impact of testosterone suppression (TS) on craniofacial growth during puberty remains inconclusive. This study aimed to evaluate the impact of TS during puberty on cephalometric measurements and histological characteristics of facial growth centers. MATERIALS AND METHODS: Thirty-six heterogenic Wistar male rats were randomly allocated into experimental orchiectomy (ORX) and control (sham) groups. At an age of 23 days (prepubertal stage), orchiectomy and placebo surgery were performed. Cephalometric measurements were performed via lateral cephalograms during and after puberty. The animals were euthanized at an age of 45 days (pubertal stage) and 73 days (postpubertal stage). Histological slices of the growth centers (condyle, premaxilla, and median palatine suture) were stained with hematoxylin and eosin, and sirius red. Student's t or Mann-Whitney U tests were used to compare linear and angular cephalometric measurements across groups (α error = 5%). RESULTS: Linear and angular measurements were statistically different in ORX animals (cranial bones, maxilla, and mandible) at 45 days and 73 days. Condylar histology showed a decrease in prechondroblast differentiation and a delay of mineralization in ORX animals. Vascularization of the medium palatine suture was lower in the ORX group at 45 days. Type I and III collagen fiber synthesis was lower in the ORX groups. In the premaxillary suture, collagen fibers were better organized in the sham groups. CONCLUSIONS: Our results suggest that testosterone suppression affects craniofacial growth during puberty.

Orthodontic pain: c-Fos expression in rat brain nuclei after rapid maxillary expansion.

BACKGROUND: The aim of this in vivo study was to quantitatively evaluate pain after rapid maxillary expansion (RME) in young rats by analyzing the activation of nociception-related structures, that is, the caudalis, interpolaris, and oralis subnuclei, according to the Fos expression. METHODS: A total of 65 Wistar rats were assigned to three groups: control group (n = 15) with no treatment, positive control group (n = 25), and experimental group (n = 25) with RME. The experimental animals were euthanized at 6, 12, 24, 48, and 72 hours after RME, and the brain was later carefully collected. Coronal sections through the spinal trigeminal caudalis, spinal trigeminal interpolaris, and spinal trigeminal oralis were cut (thickness of 40 µm) on a cryostat and processed for Fos immunohistochemistry. Images from the sections were captured under light microscopy, and ImageJ software was used to count Fos-like immunoreactive neurons. The Analysis of variance (ANOVA) and Tukey test were used for statistical analysis, and the significance level was set at 5%. RESULTS: RME induced incisor distalization and opening of the midpalatal suture, as well as neuronal activation of the spinal trigeminal nucleus. The experimental group demonstrated significantly more Fos-positive neurons in subnuclei caudalis and subnuclei interpolaris 6 hours after the maxillary expansion. The Fos immunoreactivity significantly decreased at 12 hours and increased again at 24 and 48 hours (P < 0.001). CONCLUSIONS: The RME increases the neural activation of brain regions involved in the nociception region, as determined by the Fos expression. The most intense Fos-like immunoreactive expression was detected in the brain 6 hours after the start of the palatal expansion.

Investigating the association between dental age and polymorphisms in genes encoding estrogen receptors

Abstract Background Genetic polymorphisms have been shown to influence several physiological traits, including dental and craniofacial characteristics. Understanding the clinical relevance of genetic polymorphisms in dental practice is crucial to personalize treatment plans and improve treatment outcomes. Objective to evaluate the association between dental age and genetic polymorphisms in genes encoding estrogen receptors alpha and beta (ESR1 and ESR2, respectively) in a sample of Brazilian children. Methodology This retrospective cross-sectional study was performed with children undergoing orthodontic treatment. Patients with syndromes, congenital anomalies, craniofacial deformities, under hormonal or systemic treatment, and with a previous history of facial trauma were excluded. Panoramic radiographs were used to assess dental age according to the Demirjian, Goldstein, and Tanner method. A delta [dental age-chronological age (DA-CA)] was obtained, which shows whether the patient tends to have a normal, delayed (negative values), or advanced (positive values) dental age. DNA isolated from buccal cells was used to genotype four genetic polymorphisms: rs9340799 (A>G) and rs2234693 (C>T), located in ESR1; and rs1256049 (C>T) and rs4986938 (C>T), located in ESR2. A statistical analysis was performed and values of p<0.05 indicated statistical difference. Results A total of 79 patients were included, 44 (55.70%) girls and 35 (44.30%) boys. The Demirjian, Goldstein, and Tanner method, in general, overestimated patients' age by 0.75 years. There was no difference in the delta of dental age between the sexes (p>0.05). Genetic polymorphisms in ESR1 and ESR2 were not associated with dental age (p>0.05). Conclusion The studied genetic polymorphisms in ESR1 and ESR2 were not associated with dental age in Brazilian children.

Single Nucleotides Polymorphisms in COX2 Gene and their Association with Signs and Symptoms of Teething - A Pilot Study

ABSTRACT Objective: To investigate the association between single nucleotide polymorphisms in the COX2 gene (rs689466 and rs5275) and local and systemic signs and symptoms of teething. Material and Methods: Forty-four pairs of mothers-babies/toddlers were included. Erupted primary teeth were evaluated during clinical examination. Local and systemic signs and symptoms of teething were obtained from mothers' reporting via anamnesis. Samples of buccal cells were retrieved for DNA genotyping using real-time PCR. The T-test, Chi-square test, logistic regression, and haplotype analyses were applied. Results: Almost all mothers (95.5%) reported at least one local or systemic sign and symptom of teething. The most common was increased salivation (79.5%), diarrhea (72.3 %), and fever (70.5 %). The mean number of signs and symptoms per child was higher in boys than girls (mean = 5.1; SD= 1.5; p=0.008). Sleep disturbance (p=0.03) and loss of appetite (p=0.05) were more reported in boys. The rs689466 and rs5275 were not associated with signs and symptoms of teething (p>0.05). Conclusion: The single nucleotide polymorphisms in the COX2 gene (rs689466 and rs5275) were not associated with local and systemic signs and symptoms of teething.

Factors associated with postoperative signs and symptoms in teeth with periapical lesion: a longitudinal study.

This study aimed to evaluate the association of the variables age, gender, arch position, tooth length, root canal amplitude, and periapical lesion size with the occurrence of postoperative signs and symptoms (pain, tenderness, and edema) and the use of postoperative analgesics following root canal treatment with foraminal enlargement in single-rooted teeth with apical periodontitis. This prospective longitudinal study included 105 patients requiring root canal treatment of maxillary or mandibular single-rooted teeth with periapical lesion. After root canal treatment in a single session, pain intensity and tenderness were recorded daily for 7 days and on days 14 and 30. Edema was evaluated by two independent evaluators within 48 h, 72 h, and 7 days after treatment. Ordinal and logistic regressions were performed (p < 0.05). Female gender (beta = 1.02; p < 0.01), mandibular teeth (beta = 25.50; p < 0.01), medium root canal amplitude (beta = 0.93; p = 0.03), and edema (beta = 1.88; p < 0.01) were associated with increased postoperative pain and tenderness, while the use of analgesics (beta = -1.82; p < 0.01) and time in days (beta = -0.23; p < 0.01) were associated with a decrease in these signs and symptoms. Edema was considered a risk factor for analgesic requirement (Odds Ratio [OR] = 61.46; p < 0.01). Factors such as gender, arch position, and root canal amplitude were associated with postoperative signs and symptoms. The use of analgesics was more required in edema and was associated with decreased pain.

Factors associated with postoperative signs and symptoms in teeth with periapical lesion: a longitudinal study

Abstract This study aimed to evaluate the association of the variables age, gender, arch position, tooth length, root canal amplitude, and periapical lesion size with the occurrence of postoperative signs and symptoms (pain, tenderness, and edema) and the use of postoperative analgesics following root canal treatment with foraminal enlargement in single-rooted teeth with apical periodontitis. This prospective longitudinal study included 105 patients requiring root canal treatment of maxillary or mandibular single-rooted teeth with periapical lesion. After root canal treatment in a single session, pain intensity and tenderness were recorded daily for 7 days and on days 14 and 30. Edema was evaluated by two independent evaluators within 48 h, 72 h, and 7 days after treatment. Ordinal and logistic regressions were performed (p < 0.05). Female gender (beta = 1.02; p < 0.01), mandibular teeth (beta = 25.50; p < 0.01), medium root canal amplitude (beta = 0.93; p = 0.03), and edema (beta = 1.88; p < 0.01) were associated with increased postoperative pain and tenderness, while the use of analgesics (beta = -1.82; p < 0.01) and time in days (beta = -0.23; p < 0.01) were associated with a decrease in these signs and symptoms. Edema was considered a risk factor for analgesic requirement (Odds Ratio [OR] = 61.46; p < 0.01). Factors such as gender, arch position, and root canal amplitude were associated with postoperative signs and symptoms. The use of analgesics was more required in edema and was associated with decreased pain.

Resumo Este estudo teve como objetivo avaliar a associação das variáveis idade, sexo, posição no arco, comprimento do dente, amplitude do canal radicular e tamanho da lesão periapical com a ocorrência de sinais e sintomas pós-operatórios (dor, dor ao toque e edema) e o uso de analgésicos após o tratamento endodôntico com alargamento foraminal em dentes uniradiculares com lesão periapical. Este estudo longitudinal prospectivo incluiu 105 pacientes que necessitavam de tratamento endodôntico em dentes uniradiculares superiores ou inferiores com lesão periapical. Após o tratamento do canal radicular em uma sessão, a intensidade da dor e a dor ao toque foram registradas diariamente por 7 dias e nos dias 14 e 30. O edema foi avaliado por dois avaliadores independentes dentro de 48 h, 72 h e 7 dias após o tratamento. Foram realizadas regressões ordinal e logística, e a significância estatística foi fixada em um valor de p < 0,05. Gênero feminino (beta = 1,02; p < 0.01), dentes inferiores (beta = 25,50; p < 0.01), amplitude média do canal radicular (beta = 0,93; p = 0,03) e edema (beta = 1,88; p < 0.01) foram associados ao aumento da dor e dor ao toque pós-operatória, enquanto o uso de analgésicos (beta = -1,82; p < 0.01) e o tempo em dias (beta = -0,23; p < 0.01) foram associados à diminuição desses sinais e sintomas. O edema foi considerado fator de risco para necessidade de analgésico (Odds Ratio [OR] = 61,46; p < 0.01). Fatores como sexo, posição do arco e amplitude do canal radicular foram associados aos sinais e sintomas pós-operatórios. O uso de analgésicos foi mais necessário no edema e foi associado à diminuição da dor.

Association of third molar agenesis and microdontia with genetic polymorphisms in vitamin-D-related genes.

The present study aimed to evaluate if functional genetic polymorphisms in vitamin-D-related genes are associated with third molar agenesis and third molar microdontia in German orthodontic patients. Pre-orthodontic and follow-up treatment records were evaluated for phenotype definition. Saliva samples were collected for DNA extraction. Eight potential functional genetic polymorphisms in VDR [rs731236 (TaqI), rs7975232 (ApaI), rs2228570 (FokI), and rs1544410 (BsmI)], CYP27B1 (rs4646536), CYP24A1 (rs927650), GC (rs4588), and SEC23A (rs8018720) were evaluated using real-time PCR. Comparison among the groups were performed (third molar anomaly vs. control; third molar agenesis vs. control; and third molar microdontia vs. control) with an alpha of 5%. A total of 164 patients were analyzed. Forty-nine (29.9%) patients had at least one third molar anomaly. In the haplotype analysis, genetic polymorphisms in VDR and CYP27B1 were associated with third molar anomalies (p < 0.05). The G allele in rs8018720 (SEC23A) was more frequent in microdontia cases. In the genotype distribution analysis, rs8018720 in SEC23A was associated with third molar microdontia in the co-dominant (p = 0.034; Prevalence Ratio [PR]=5.91, 95% Confidence Interval [CI]= 1.14-30.66) and in the recessive (p = 0.038; PR=5.29; 95% CI= 1.09-25.65) models. In conclusion, vitamin D-related genes could be involved in third molar anomalies.

Transforming Growth Factor Beta Receptor 2 (TGFBR2) Promoter Region Polymorphisms May Be Involved in Mandibular Retrognathism.

Skeletal malocclusions are common phenotypes in humans and have a strong influence on genetic factors. Transforming growth factor beta (TGFß) controls numerous functions of the human body, including cell proliferation, differentiation, and migration. Thus, this study is aimed at evaluating whether genetic polymorphisms in TGFB1 and its receptor TGFBR2 are associated with mandibular retrognathism in German children and adolescents. Children and teenagers older than 8 years in the mixed or permanent dentition were included in this study. Patients with syndromes and facial trauma and patients with congenital alterations were excluded. Digital cephalometric tracings were performed using the anatomical landmarks point A, point B, sella (S), and nasion (N). Patients that have a retrognathic mandible (SNB < 78°) were selected as case group, and the patients with an orthognathic mandible (SNB = 78°- 82°) were selected as the control group. Genomic deoxyribonucleic acid (DNA) from saliva was used to evaluate four genetic polymorphisms in TGFB1 (rs1800469 and rs4803455) and TGBR2 (rs3087465 and rs764522) using real-time PCR. Chi-square or Fisher exact tests were used to compare gender, genotype, and allele distribution among groups. Genotype distribution was calculated in an additive and recessive model. Haplotype analysis was also performed. The established alpha of this study was 5%. A total of 146 patients (age ranging from 8 to 18 years) were included in this epidemiological genetic study. The genetic polymorphism rs3087465 in TGFBR2 was associated with mandibular retrognathism. Carrying the AA genotype in the rs3087465 polymorphism decreased the chance of having mandibular retrognathism (odds ratio = 0.25, confidence interval 95% = 0.06 to 0.94, p = 0.045). None of the haplotypes was associated with mandibular retrognathism (p > 0.05). In conclusion, we found that the genetic polymorphism rs3087465 in the promoter region of the TGFBR2 was associated with mandibular retrognathism in Germans.

Evaluation of composite restorations in primary molars subjected to selective caries removal associated with antimicrobial photodynamic therapy: A randomized controlled trial.

BACKGROUND: Antimicrobial photodynamic therapy (aPDT) has been used as an adjunct treatment of deep caries lesions; however, studies on the effects of aPDT on the longevity of restorations are still limited. AIM: To evaluate the clinical performance of composite restorations in primary molars subjected to selective caries removal (SCR) associated with aPDT. DESIGN: A randomized clinical trial was designed. Primary molars of patients (mean age 6.15 years) with deep caries lesions without signs and symptoms of pulpal involvement were selected. A total of 64 teeth were randomly divided into groups G1 (SCR, 32 teeth) and G2 (SCR + aPDT, 32 teeth) for treatment, restored with composite, and evaluated after a week (T0 ), 6 months (T1 ), and 12 months (T2 ) according to the criteria of FDI. Groups were compared using the Rao-Scott chi-squared test and the logistic regression analysis for complex designs to account for multiple observations per subject (alpha = 0.05). RESULTS: From all FDI criteria evaluated, the marginal adaptation for the SCR + aPDT group was significantly better in comparison with the SCR group at T0 and T2 in the logistic regression analysis (T0: OR = 0.151; 95% CI = 0.03-0.068, P = .015; and T2: OR = 0.201; 95% CI = 0.05-0.79, P = .022). CONCLUSION: The marginal adaptation of primary molar resin restorations was positively affected by aPDT after 12 months of follow-up.

Photobiomodulation impacts the levels of inflammatory mediators during orthodontic tooth movement? A systematic review with meta-analysis.

During orthodontic tooth movement (OTM), there is the release of cytokines in the gingival crevicular fluid (GCF) that are supposed to participate in the bone remodeling. This systematic review aimed at assessing the effects of photobiomodulation (PBM) on the levels of these cytokines during OTM. This systematic review according to Cochrane Collaboration guidelines aimed to answer the clinical question following the PICOS strategy. The broad search in the literature was performed before 05 April, 2021 in six electronic databases (Pubmed, Web of Science, Scopus, Embase, Cochrane, Biblioteca Virtual de Saúde) and supplemented by the grey literature. The risk of bias of randomized and non-randomized clinical trials was evaluated by two tools: RoB 2 and ROBINS-I. Mean and standard deviation of cytokine levels was extracted to meta-analysis, and the GRADE system was applied to assess the quality of the evidence. Nine studies were included in this review. Low-level laser therapy (LLLT) was the photobiomodulation type used in most of the studies (n = 8). The wavelengths used varied from 618 to 980 nm and also differed concerning the light emission pattern. LLLT increased the levels of IL-1ß, IL-8, OPN, and PGE2, but not TNF-α1, TGF-ß1. The levels of IL6, RANKL, and OPG presented conflicting results. LLLT was statistically associated with an increase of IL-1ß levels (standard mean difference [SMD] = 1.99; 95% confidence interval = 0.66 to 3.33; p < 0.001) with low certainty of evidence. LLLT may increase the levels of IL-1ß and other cytokines; however, the results should be interpreted with caution due to protocol variations between studies, and the few studies added in the meta-analysis.

Lack of association between delayed tooth emergence and single nucleotide polymorphisms in estrogen receptors

Abstract The purpose of the study was to investigate the association between single nucleotide polymorphisms (SNPs) in genes encoding estrogen receptors (ESR1 and ESR2, respectively) and delayed tooth emergence (DTE). This cross-sectional study was composed of biological unrelated children of both sexes, age ranging from 11 to 13 years old. DTE was defined when the successor primary tooth was still present in the oral cavity after its exfoliation time or the absence of the permanent tooth emergence into the oral cavity. Children were diagnosed with DTE when they had at least one delayed permanent tooth, according to age of exfoliation of each tooth proposed by The American Dental Association. Genomic DNA from saliva was used to evaluate the SNPs in ESR1 (rs9340799 and rs2234693) and ESR2 (rs1256049 and rs4986938) using Real-Time PCR. Chi-square or Fisher exact tests and Logistic Regression adjusted by age and gender were performed. SNP-SNP interaction was accessed by multifactor dimensionality reduction (MDR) analysis also adjusted by gender and age. The established alpha of this study was 5%. Among 537 included children, 296 (55%) were in the "DTE" group and the 241 (45%) were in the "Control" group. Age and gender were not statistically different among the groups (p>0.05). Genotype distribution of the SNPs rs9340799, rs2234693, rs1256049 and rs4986938 were not associated with DTE (p> 0.05). The models elected by MDR were not statistically significant either. Conclusions: The studied SNPs in ESR1 and ESR2 were not associated with permanent DTE.

RESUMO O objetivo do presente estudo foi investigar a associação entre polimorfismos de nucleotídeo único (SNPs) em genes que codificam receptores de estrógeno (ESR1 e ESR2, respectivamente) e o retardo na emergência dentária (DTE). Este estudo transversal foi composto por crianças biológicas não relacionadas de ambos os sexos, com idades entre 11 e 13 anos. O DTE foi definido pela presença do dente decíduo na cavidade bucal após seu tempo e também, quando as crianças apresentaram pelo menos um dente permanente com atraso. O DNA genômico foi usado para avaliar os SNPs em ESR1 (rs9340799 e rs2234693) e ESR2 (rs1256049 e rs4986938) usando PCR em tempo real. Foram realizados testes Qui-quadrado ou exato de Fisher e Regressão Logística ajustados por idade e sexo. A interação SNP-SNP foi acessada pela análise de redução de dimensionalidade multifatorial (MDR), também ajustada por sexo e idade. O alfa de 5% foi estabelecido. Entre 537 crianças incluídas, 296 (55%) estavam no grupo "DTE" e 241 (45%) estavam no grupo "Controle". A idade e o sexo não foram estatisticamente diferentes entre os grupos (p> 0,05). A distribuição de genótipos dos SNPs rs9340799, rs2234693, rs1256049 e rs4986938 não foi associada ao DTE (p> 0,05). Os modelos eleitos pelo MDR também não foram estatisticamente significativos. Conclusões: Os SNPs estudados na ESR1 e ESR2 não foram associados ao DTE na dentição permanente.

Exploring the Association Between Genetic Polymorphisms in Genes Involved in Craniofacial Development and Isolated Tooth Agenesis.

Tooth agenesis is a common congenital anomaly in humans and is more common in oral cleft patients than in the general population. Many previous studies suggested that oral cleft and tooth agenesis share a similar genetic background. Therefore, this study explored the association between isolated tooth agenesis and genetic polymorphisms in genes that are crucial for craniofacial and tooth development. Panoramic radiographs, anamnesis, and genomic DNA from 273 patients were included. Patients were classified as tooth agenesis present, when at least one permanent tooth was congenitally missing. Patients with syndromes and oral cleft were excluded. Only unrelated patients were included. The genetic polymorphisms in BMP2 (rs235768 and rs1005464), BMP4 (rs17563), RUNX2 (rs59983488 and rs1200425), and SMAD6 (rs3934908 and rs2119261) were genotyped by real-time polymerase chain reaction. Genotype and allele distributions were compared between the tooth agenesis phenotypes and controls by Chi-square test. Haplotype and diplotype analysis were also performed, in addition to multivariate analysis (alpha of 0.05). A total of 86 tooth agenesis cases and 187 controls were evaluated. For the rs235768 in BMP2, patients carrying TT genotype have higher chance to present tooth agenesis [p < 0.001; prevalence ratio (PR) = 8.29; 95% confidence interval (CI) = 4.26-16.10]. The TT genotype in rs3934908 (SMAD6) was associated with higher chance to present third molar agenesis (p = 0.023; PR = 3.25; 95% CI = 1.17-8.99). BMP2 was also associated in haplotype and diplotype analysis with tooth agenesis. In conclusion, genetic polymorphisms in BMP2 and SMAD6 were associated with isolated tooth agenesis.

Parathyroid Hormone Gene and Genes Involved in the Maintenance of Vitamin D Levels Association with Mandibular Retrognathism.

In this study we evaluated whether single nucleotide polymorphisms (SNPs) in the genes encoding PTH, VDR, CYP24A1, and CYP27B1 were associated with mandibular retrognathism (MR). Samples from biologically-unrelated Brazilian patients receiving orthodontic treatment were included in this study. Pre-orthodontic lateral cephalograms were used to determine the phenotype. Patients with a retrognathic mandible were selected as cases and those with an orthognathic mandible were selected as controls. Genomic DNA was used for genotyping analysis of SNPs in PTH (rs694, rs6256, and rs307247), VDR (rs7975232), CYP24A1 (rs464653), and CYP27B1 (rs927650). Chi-squared or Fisher's tests were used to compare genotype and allele distribution among groups. Haplotype analysis was performed for the SNPs in PTH. The established alpha was p < 0.05. Multifactor dimensionality reduction (MDR) was used to identify SNP-SNP interactions. A total of 48 (22 males and 26 females) MR and 43 (17 males and 26 females) controls were included. The linear mandibular and the angular measurements were statistically different between MR and controls (p < 0.05). In the genotype and allele distribution analysis, the SNPs rs694, rs307247, and rs464653 were associated with MR (p < 0.05). MDR analyses predicted the best interaction model for MR was rs694-rs927650, followed by rs307247-rs464653-rs927650. Some haplotypes in the PTH gene presented statistical significance. Our results suggest that SNPs in PTH, VDR, CYP24A1, and CYP27B1 genes are associated with the presence of mandibular retrognathism.

Lack of association between delayed tooth emergence and single nucleotide polymorphisms in estrogen receptors.

The purpose of the study was to investigate the association between single nucleotide polymorphisms (SNPs) in genes encoding estrogen receptors (ESR1 and ESR2, respectively) and delayed tooth emergence (DTE). This cross-sectional study was composed of biological unrelated children of both sexes, age ranging from 11 to 13 years old. DTE was defined when the successor primary tooth was still present in the oral cavity after its exfoliation time or the absence of the permanent tooth emergence into the oral cavity. Children were diagnosed with DTE when they had at least one delayed permanent tooth, according to age of exfoliation of each tooth proposed by The American Dental Association. Genomic DNA from saliva was used to evaluate the SNPs in ESR1 (rs9340799 and rs2234693) and ESR2 (rs1256049 and rs4986938) using Real-Time PCR. Chi-square or Fisher exact tests and Logistic Regression adjusted by age and gender were performed. SNP-SNP interaction was accessed by multifactor dimensionality reduction (MDR) analysis also adjusted by gender and age. The established alpha of this study was 5%. Among 537 included children, 296 (55%) were in the "DTE" group and the 241 (45%) were in the "Control" group. Age and gender were not statistically different among the groups (p>0.05). Genotype distribution of the SNPs rs9340799, rs2234693, rs1256049 and rs4986938 were not associated with DTE (p> 0.05). The models elected by MDR were not statistically significant either. Conclusions: The studied SNPs in ESR1 and ESR2 were not associated with permanent DTE.

Potential interactions among single nucleotide polymorphisms in bone- and cartilage-related genes in skeletal malocclusions.

OBJECTIVE: To investigate SNPs in bone- and cartilage-related genes and their interaction in the aetiology of sagittal and vertical skeletal malocclusions. SETTINGS AND SAMPLE POPULATION: This study included 143 patients and classified as follows: skeletal class I (n = 77), class II (n = 47) and class III (n = 19); maxillary retrusion (n = 39), protrusion (n = 52) and well-positioned maxilla (n = 52); mandibular retrognathism (n = 50), prognathism (n = 50) and well-positioned mandible (n = 43); normofacial (n = 72), dolichofacial (n = 55) and brachyfacial (n = 16). MATERIALS AND METHODS: Steiner's ANB, SNA, SNB angles and Ricketts' NBa-PtGn angle were measured to determine the skeletal malocclusion and the vertical pattern. Nine SNPs in BMP2, BMP4, SMAD6, RUNX2, WNT3A and WNT11 were genotyped. Chi-squared test was used to compare genotypes among the groups. Multifactor dimensionality reduction (MDR) and binary logistic regression analysis, both using gender and age as co-variables, were also used. We performed Bonferroni correction for multiple testing. RESULTS: Significant associations at P < .05 were observed for SNPs rs1005464 (P = .042) and rs235768 (P = .021) in BMP2 with mandibular retrognathism and for rs59983488 (RUNX2) with maxillary protrusion (P = .04) as well as for rs708111 (WNT3A) with skeletal class III (P = .02; dominant model), rs1533767 (WNT11) with a brachyfacial skeletal pattern (P = .01, OR = 0.10; dominant model) and for rs3934908 (SMAD6) with prognathism (P = .02; recessive model). After the Bonferroni correction, none of the SNPs remained associated. The MDR predicted some interaction for skeletal class II, dolichofacial and brachyfacial phenotypes. CONCLUSION: Our results suggest that SNPs in BMP2, BMP4, SMAD6, RUNX2, WNT3A and WNT11 could be involved in the aetiology of sagittal and vertical malocclusions.

Genetic polymorphisms in interleukin-6 and interleukin-1-beta were associated with dental caries and gingivitis.

OBJECTIVE: Evaluate the association between single nucleotide polymorphisms (SNPs) in Interleukin-6 (IL-6) gene (rs1800795) and in Interleukin-1-beta (IL-1ß) gene (rs1143627 and rs1143629) with dental caries and gingivitis in Brazilian children. MATERIAL AND METHODS: Three hundred and fifty-three children aged 8-11 years were included. Visible biofilm and gingival bleeding were evaluated by Community Periodontal Index. The International System for Detection and Assessment of Carious Lesions (ICDAS) was used to investigate dental caries. Real-time PCR evaluated SNPs in the DNA. Chi-square test, haplotype analysis and logistic regression were applied (alpha of 5%). RESULTS: The GG genotype in rs1800795 (IL-6) decreases the risk of gingivitis in a co-dominant model (p = .05; OR = 0.64). The GG genotype in rs1143627 (IL-1ß) reduces the risk of dental caries (Co-dominant model: ICDAS0 versus ICDAS1-6: p = .05; OR = 0.55. ICDAS0-2 versus ICDAS3-6: p = .02; OR = 0.49. Recessive model: ICDAS0 versus ICDAS1-6: p = .005; OR = 0.48. ICDAS0-2 versus ICDAS3-6: p = .004; OR = 0.45. Logistic regression: ICDAS0-2 versus ICDAS3-6: p = .05; OR = 0.24; CI 95%= 0.05-1.00). The GG genotype in rs1143629 was more frequent in ICDAS0 (p = .05; OR: 0.60). In the haplotype analysis, IL-1ß was associated with gingivitis. CONCLUSION: The rs1800795 in IL-6 gene was associated with gingivitis. The rs1143627 and rs1143629 in IL-1ß were associated with dental caries and gingivitis.

Investigation of Genetic Polymorphisms in BMP2, BMP4, SMAD6, and RUNX2 and Persistent Apical Periodontitis.

INTRODUCTION: This study aimed to evaluate the interplay among single-nucleotide polymorphisms (SNPs) in the encoding genes BMP2, BMP4, SMAD6, and RUNX2 in persistent apical periodontitis (PAP). METHODS: In this multicentric study, 272 patients diagnosed with pulp necrosis with apical periodontitis before root canal therapy who attended regular follow-up visits for at least 1 year were screened. Periapical radiographs and clinical aspects were evaluated, and the participants were classified as PAP (n = 110) or repaired (n = 162). Genomic DNA was used for the genotyping of the following SNPs: rs1005464 and rs235768 in bone morphogenetic protein 2 (BMP2), rs17563 in bone morphogenetic protein 4 (BMP4), rs2119261 and rs3934908 in SMAD family member 6 (SMAD6), and rs59983488 and rs1200425 in runt-related transcription factor 2 (RUNX2). The chi-square test was used to compare genotype distributions between groups. The multifactor dimensionality reduction method was applied to identify SNP-SNP interactions. The alpha for all the analysis was 5%. RESULTS: The multifactor dimensionality reduction suggested the rs235768 in BMP2 and rs59983488 in RUNX2 as the best SNP-SNP interaction model (cross-validation = 10/10, testing balanced accuracy = 0.584, P = .026) followed by rs17563 in BMP4 and rs2119261 in SMAD6 (cross validation = 10/10, testing balanced accuracy = 0.580, P = .031). In the rs235768 in BMP2 and rs59983488 in RUNX2 model, the high-risk genotype was TT + TT (odds ratio = 4.36; 95% confidence interval, 0.44-42.1). In model rs17563 in BMP4 and rs2119261 in SMAD6, GG + TT (odds ratio = 2.63; 95% confidence interval, 0.71-11.9) was the high-risk genotype. CONCLUSIONS: The interactions between rs235768 in BMP2 and rs59983488 in RUNX2 and between rs17563 in BMP4 and rs2119261 in SMAD6 are associated with PAP, suggesting that an interplay of these SNPs is involved in the higher risk of developing PAP.

Association between P561T polymorphism in growth hormone receptor gene and mandibular prognathism: systematic review and metaanalysis

Objective: Through a systematic review and meta-analysis, the aim this study was evaluating the association between the P561T polymorphism in GHR (rs6184) with skeletal Class III malocclusion in different populations. Methods: A broad search for studies was conducted using the databases: PubMed, Web of Science, Scopus, Cochrane, Google Scholar and Open Grey until December 2018. The study design according to PECOS was: P-Orthodontic patients; E- polymorphism P561T in GHR; C- absence of polymorphism P561T in GHR; O- linear dimension alterations in maxilla and mandibular measurements; S- Cross-sectional studies. The selected studies were qualified by 10-point scoring sheet methodological quality. The subgroups evaluation was performd according to the linear measurements evaluated in two or more studies, as follows: body height, N-S, A'-PTM', Gn-Go, Pog'-Go, and Co-Go.A fixed effect model was used and the mean differences were performed using the inverse-variance meta-analysis. The I2 (95%) was used to measure statistical heterogeneity between studies, where I2 values of 25%, 50%, and 75% signified low, medium, and high heterogeneity, respectively. Results: The initial search identified 146 studies. After excluding duplicate abstracts, 138 were selected. Seven studies were included in the systematic review. Only one study was classified as having low methodological quality. Three studies were included in the meta-analysis. The meta-analysis demonstrated an association between the Co-Go linear measure and CC genotype (p<0.0001), with a mean difference and confidence interval of 3.79 [2.06, 5.52]. CC was associated with greater mandibular height. Conclusion: The polymorphism P561T in GHR is associated with Co-Go measurement in Asians, with low level of evidence.

Objetivo: Por meio de uma revisão sistemática e meta-análise, o objetivo deste estudo foi avaliar a associação entre o polimorfismo P561T em GHR (rs6184) com a maloclusão de Classe III esquelética em diferentes populações. Métodos: Uma ampla pesquisa de estudos foi realizada utilizando os bancos de dados PubMed, Web of Science, Scopus, Cochrane, Google Scholar e Open Grey até dezembro de 2018. O desenho do estudo de acordo com o PECOS foi: P-Pacientes ortodônticos; Polimorfismo P561T em GHR; Causência de polimorfismo P561T em GHR ; O-alterações na dimensão linear das medidas maxilares e mandibulares; S- Estudos transversais. Os estudos selecionados foram qualificados pela qualidade metodológica em uma escala de 10 pontos. A avaliação emsubgrupos. O subgrupo foi realizada de acordo com as medidas lineares avaliadas em dois ou mais estudos, como a seguir: altura corporal, N-S, A'-PTM ', Gn-Go, Pog'-Go. Foi utilizado o modelo de efeito fixo e as diferenças médias foram realizada usando a metanálise de variância inversa. O I2 (95%) foi utilizado para medir heterogeneidade estatística entre estudos, em que valores de I2 de 25%, 50% e 75% significaram baixa, média e alta heterogeneidade, respectivamente. Resultados: A pesquisa inicial identificou 146 estudos. Após excluir resumos duplicados, 138 foram selecionados. Sete estudos foram incluídos na revisão sistemática. Apenas 1 estudo foi classificado como de baixa qualidade metodológica. Três estudos foram incluídos na meta-análise. A metaanálise demonstrou uma associação entre a medida linear Co-Go e o genótipo CC (p<0,0001), com diferença média e intervalo de confiança de 3,79 [2,06; 5,52]. CC foi associado com maior altura mandibular. Conclusão: O polimorfismo P561T em GHR está associado à medida Co-Go em asiáticos, com baixo nível de evidência.