Polymorphisms in hormonal-related genes might be associated with variations in permanent tooth crown size.

BACKGROUND: The variability in tooth crown size (TCS) is influenced by genetic factors and might be regulated by the difference in hormonal response. MATERIALS AND METHODS: This study aimed to evaluate the association between variations in TCS of permanent teeth with associated factors and genetic polymorphisms in hormonal-related genes (ESR1, ESR2 and PTH). This cross-sectional study involved dental casts from 86 individuals of both sexes. Dental casts were used to determine the maximum TCS of all fully erupted permanent teeth (except third molars) in the mesiodistal (MD) and buccolingual (BL) dimensions. Data such as sex, ethnicity, dental group (incisor, canine, premolar and molar), dental arch (upper and lower) and genetic polymorphisms of hormonal-related genes were used. The DNA from each patient was collected to evaluate the genetic polymorphisms in ESR1 (rs2234693 and rs9340799), ESR2 (rs1256049 and rs4986938) and PTH (rs694, rs6256 and rs307247) through real-time PCR. The data were submitted to statistical analysis with a significance level of 0.05. RESULTS: In the MD dimension, the sex, dental group and dental arch were associated with variation in TCS (P < .05). In the BL dimension, the sex, dental group, dental arch and polymorphism in rs694 and rs307247 were associated with variation in TCS. CONCLUSIONS: In short, this study suggests that genetic polymorphisms of PTH are associated with variations in the BL TCS of permanent human teeth.

Genetic polymorphisms are involved in oral health-related quality of life in skeletal class III patients submitted to orthognathic surgery.

OBJECTIVE: This study aimed to evaluate whether sex and genetic polymorphisms impact the oral health-related quality of life (OHRQoL) preoperatively and the difference between preoperative and postoperative OHRQoL in skeletal Class III patients submitted to orthognathic surgery. MATERIALS AND METHODS: This longitudinal study consisted of ninety-nine patients with skeletal Class III malocclusion who required orthognathic surgery. The Oral Health Impact Profile-14 (OHIP-14) is a questionnaire used to assess the OHRQoL with a 5-point Likert-type scale, covering seven domains related to physical and psychosocial factors. The questionnaire was applied in the preoperative and postoperative periods, and the difference scores were calculated to assess the OHRQoL after orthognathic surgery. The DNA was extracted from oral mucosa cells to evaluate genetic polymorphisms in ANKK1, DRD2, ESR1, and ESR2 through real-time PCR. RESULTS: There was an improvement in all OHRQoL domains following orthognathic surgery (p < 0.05). In the preoperative evaluation, women presented worse OHRQoL (p < 0.05) than men. There was no statistical difference between sex and the OHRQoL after surgery (p > 0.05). When evaluating the polymorphisms and preoperative OHIP-14 scores, CT genotype patients for rs1800497 (ANKK1) had a worse perception of the physical pain domain than CC genotype (p = 0.026), and CC genotype patients for rs1256049 (ESR2) had a worse perception of the functional limitation domain than CT genotype (p = 0.002). In the analysis between polymorphisms and postoperative and preoperative difference scores, CT genotype patients for rs1256049 (ESR2) had a greater improvement in the perception of the physical pain domain than the CC genotype (p = 0.031). In rs6275 and rs6276 (DRD2), patients with the CC genotype worsened the perception of the functional limitation domain than the TT genotype (p = 0.045), and AA genotype patients worsened the perception of the functional limitation domain than GG genotype (p = 0.048) after surgery, respectively. In addition, patients with the CT genotype for rs1800497 (ANKK1) had a greater improvement of OHRQoL perception in the total scale than the TT genotype (p = 0.018), and CT genotype patients had a greater improvement in the perception of function limitation domain than TT genotype (p = 0.017). CONCLUSION: Women have a worse perception of OHRQoL in the preoperative period of orthognathic surgery. Furthermore, polymorphisms in the ANKK1, DRD2, and ESR2 genes could be involved with OHRQoL in the preoperative period and following orthognathic surgery. CLINICAL RELEVANCE: The knowledge of the genetic background concerning OHRQoL in skeletal class III patients would aid in clinical practice to screen for associated genetic factors and prevent OHRQoL deterioration, especially after orthognathic surgery, considering that patients' genetic profiles would soon be available.

Vertical Bonegraft Wrap-A Technique to Increase Soft Tissue Volume in Paranasal Region.

This study presents a technique to gain soft tissue volume in the paranasal region, using a xenogenous bonegraft wrap with a porcine pericardium collagen membrane in a patient with severe paranasal deficiency and midfacial hypoplasia. The technique consisted of using particulate bonegraft that is wrapped on collagen membrane and placed vertically and parallel to the lateral wall of the nasal cavity, over maxillary osteotomies. In a tomographic analysis of linear and volumetric measurements with 14 days and 6 months after the procedure, it was observed good stability of the vertical bonegraft wrap, as well as volume gain in the paranasal region and low absorption rate of the grafted material. This technique presented a satisfactory clinical result, promoting an improvement in facial harmony with gain volume in the paranasal region, guaranteeing greater predictability in the treatment of a patient with significant maxillary advancement surgery.

Genetic Polymorphisms of Estrogen Receptors α and ß are Associated with Craniofacial Measurements in Patients With Dentofacial Deformity.

Dentofacial deformities are characterized by abnormalities in craniofacial development that affects the individual's skeletal and occlusion, often causing functional and esthetic problems. In literature, there is an involvement of polymorphisms in estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) genes in craniofacial measurements. The aim of this study was to evaluate a possible association between polymorphisms in ESR1 (rs2234693 and rs9340799) and ESR2 (rs1256049 and rs4986938) genes with cephalometric measurements in individuals with dentofacial deformities. This cross-sectional study was performed with 158 individuals in the preoperative period of orthognathic surgery. The cephalometric measurements obtained through lateral cephalogram using Dolphin Imaging software. For genetic analysis, the DNA extracted from epithelial cells of the oral mucosa and were genotyped using the real-time polymerase chain reaction. The data found submitted to statistical analysis, through the Kolmogorov-Smirnov, Mann-Whitney, and Kruskal-Wallis tests, using the IBM SPSS software version 24.0. Considered a significance level of 0.05. We found association between polymorphisms and cephalometric measurements just in the female sex. The polymorphisms ESR1/rs9340799 ( P= 0.003), ESR1/rs2234693 ( P= 0.026), and ESR2/rs1256049 ( P= 0.046) were associated with the upper gonial angle (Ar-Go-N). The polymorphism ESR2/rs1256049 was also associated with the facial axis-rickets (NBa-PtGn) ( P= 0.004), anterior cranial base (SN) ( P= 0.036), and Y-axis (SGn-SN) ( P= 0.031).

Breastfeeding and Cleft Lip and Palate: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the association between cleft lip and/or cleft palate (CL/P) and breastfeeding (BF). DESIGN: A systematic review and meta-analysis were performed based on studies published in PubMed, Scopus, Web of Science, Cochrane Library, LILACS, BBO, and Embase databases, and in the gray literature. The search occurred in September 2021 and was updated in March 2022. Observational studies evaluating the association between BF and CL/P were included. Risk of bias was analyzed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was conducted. Certainty of evidence was evaluated using the GRADE approach. MAIN OUTCOME MEASURE(S): Frequency of BF in relation to the presence or absence of CL/P, as well as to the type of CL/P. The association between cleft type and BF challenges was also evaluated. RESULTS: From a total of 6863 studies identified, 29 were included in the qualitative review. Risk of bias was moderate and high in most studies (n = 26). There was a significant association between the presence of CL/P and absence of BF (OR = 18.08; 95% CI 7.09-46.09). Individuals with cleft palate with or without cleft lip (CP ± L) had a significantly lower frequency of BF (OR = 5.93; 95% CI 4.30-8.16) and a significantly higher frequency of BF challenges (OR = 13.55; 95% CI 4.91-37.43) compared to individuals with CL. Certainty of the evidence was low or very low in all analyses. CONCLUSION: The presence of clefts, especially those with palate involvement, is associated with higher chances of absence of BF.

Ethnic Differences in the Brazilian Population Influence the Impact of BMP4 Genetic Variants on Susceptibility of Nonsyndromic Orofacial Clefts.

OBJECTIVE: The study evaluated the association of BMP4 tag-SNPs and SNP-SNP interactions involving genes active by BMP4 pathway during craniofacial development in the susceptibility of nonsyndromic orofacial clefts (NSOC) in the Brazilian population. DESIGN: Case-control study. SETTING: Brazilian Oral Cleft Group. PARTICIPANTS: The study included 881 healthy controls and 800 patients with different types of NSOC: 232 with cleft lip only (NSCLO), 568 with cleft lip and palate (NSCLP), and 274 with cleft palate only (NSCPO). INTERVENTIONS: The genomic DNA was genotyped with allelic discrimination assays for five BMP4 tag-SNPs (rs11623717, rs17563, rs2071047, rs2761887 and rs4898820), and analyzed their allelic and genotypic associations using multiple logistic regression. The interactions of these variants with genes involved in the BMP4 signaling pathway, including FGFR1, GREM1, NOG, VAX1 and the 4p16.2 locus, were explored. MAIN OUTCOME MEASURES: BMP4 variants in the NSOC risk. RESULTS: Although only nominal p values were identified when the whole sample was considered, subgroup analysis including the patients with high African genomic ancestry showed significant associations of rs2761887 with risk for nonsyndromic cleft lip with or without cleft palate (NSCL ± P)[(ORhom: 2.16; 95% CI: 1.21-3.85; p = 0.01) and (ORrec: 2.05; 95% CI: 1.21-3.47; p = 0.006)]. Thirteen significant SNP-SNP interactions involving BMP4 and the SNPs at FGFR1, GREM1, NOG and VAX1 and at locus 4p16.2 for increased risk of NSCL ± P were identified. CONCLUSIONS: Our results demonstrate an increased risk of NSCL ± P in Brazilian individuals with enrichment of African ancestry in the presence of the BMP4 rs2762887 polymorphism, and reveal relevant genetic contribution of SNP-SNP epistatic interactions involving BMP4 variants to NSCL ± P risk.

Isolated nonsyndromic cleft palate: multicenter epidemiological study in the Brazil.

BACKGROUND: Nonsyndromic orofacial clefts (NSOC) are the craniofacial most common congenital malformations. There are evidences that the nonsyndromic cleft palate (NSCP) development differs from other NSOC. However, most of the publications treat NSCP without considering that information. Furthermore, few studies focus on NSCP. The aim of this study was to describe epidemiological findings of patients with isolated NSCP in Brazil. METHODS: In this cross-sectional multicenter study, four reference Centers for treatment in three different Brazilian states was investigated. Data were obtained from clinical records of patients, between November 2021 and June 2022. Researched variables were sociodemographic, clinical characteristics and pregnancy and family history. Pearson's chi-square and ANOVA One-way tests were used for associations. RESULTS: Majority were female (58.1%), white (60.7%) with incomplete NSCP (61.2%). There was an association between complete NSCP and a positive history of medical problems during pregnancy (p = 0.016; 27.9%; OR: 1.94; 1.12-3.35). Systemic alterations were perceived in 40.6% of the sample with odds ratio for development of the complete type (OR: 1.21; 0.74-1.97). Higher OR was visualized in medication use during pregnancy (OR: 1.35; 0.76-2.37) and positive family history of oral cleft (OR: 1.44; 0.80-2.55). Dental and surgical care was associated with higher age groups (p < 0.050). CONCLUSIONS: NSCP was most prevalent in white skin color female. Complete NSCP is associated with medical problems during pregnancy. Medication use during pregnancy and positive family history of oral cleft increase the chance of developing complete NSCP.

Variation of Tooth Crown Size in Cleft Lip and Palate Patients.

AIM: This study aims to compare the mesiodistal (MD) and buccolingual (BL) tooth crown size (TCS) of adult patients with cleft lip and palate (CL/P) and patients without CL/P. MATERIALS AND METHODS: The sample of this study consisted of 146 adult patients, of both genders, of which 73 were included in the case group (with CL/P) and 73 were included in the control group (without CL/P). Data regarding gender and age and cleft type were collected. In addition, dental models were evaluated to obtain the TCS in the maximum distance of the MD and BL dimensions of all erupted permanent teeth (except third molars). The results were submitted to statistical analysis with a significance level of 0.05. RESULTS: In the upper arch, the central incisors (CI) were smaller in the case group for the MD and BL dimensions (p < 0.05). The lateral incisors (LI) and canine (C) were smaller only in the BL width (p < 0.05) and the second molars (SM), were smaller only in the MD dimensions. In the lower arch, there were significant differences only in the BL width between groups, the CI and LI presented smaller measurements in CL/P patients, while the left first molar (FM) and right first premolar (FPM) were larger (p < 0.05) than in patients without CL/P. CONCLUSION: Patients with CL/P have different sizes in certain teeth compared to patients without CL/P. CLINICAL RELEVANCE: Cleft lip and palate patients usually present important dental anomalies; thereby, the knowledge about trends in tooth size variations in CL/P patients can aid in dental and orthodontic treatment planning to obtain a stable, functional, and esthetic occlusion.

Tooth abnormalities associated with non-syndromic cleft lip and palate: systematic review and meta-analysis.

OBJECTIVE: To evaluate the association between orofacial clefts (OFC) and tooth abnormalities (TA). METHODS: We searched PubMed, Scopus, Web of Science, Cochrane Library, LILACS, and BBO, and in the gray literature and selected observational studies that evaluated the association between TA and OFC. The risk of bias was analyzed using the Newcastle-Ottawa Scale. A random-effects meta-analysis was performed comparing the presence and absence of OFC, cleft type-cleft palate (CP) and cleft lip with or without palate (CL/P)-and cleft laterality-unilateral and bilateral. The certainty of evidence was evaluated using the GRADE approach. RESULTS: A total of 99 studies were included in the qualitative analysis, and 37 were included in the meta-analysis. Only four studies were classified as low risk of bias. Significant associations were observed between the presence of OFC and tooth agenesis (OR = 19.46; 95%CI = 4.99-75.96), supernumerary teeth (OR = 4.04; 95%CI = 1.26-12.99), developmental defects of enamel (OR = 3.15; 95%CI = 1.28-7.80), microdontia (OR = 15.57; 95%CI = 1.06-228.51), and taurodontism (OR = 1.74; 95%CI = 1.74-2.86). Individuals with CP had a lower frequency of supernumerary teeth (OR = 0.22; 95%CI = 0.08-0.64), peg-shaped tooth (OR = 0.31; 95%CI = 0.12-0.80), and morphological TA (OR = 0.13; 95%CI = 0.04-0.45) than individuals with CL/P. No TA was significantly associated with cleft laterality (p > 0.05). The quality of the evidence was very low in all analyses. CONCLUSION: Individuals with OFC had a higher frequency of TA than those without OFC. Individuals with CP had a lower frequency of TA than individuals with CL/P. No TA was associated to cleft laterality. CLINICAL RELEVANCE: Help to identify the treatment needs of individuals affected by OFC, improving the services provided to this population.

Quality of Life and Temporomandibular Disorders in Patients With Skeletal Class III Malocclusion With Cleft Lip and Palate.

OBJECTIVE: The aim of the study was to assess the quality of life (QOL), oral health-related QOL (OHRQOL), temporomandibular disorders (TMDs), and psychological factors in patients with skeletal Class III malocclusion with cleft lip and palate (CLP) and without CLP. DESIGN: Case-control. SETTING: Primary care, institutional practice. PATIENTS: One hundred thirty-six patients with skeletal Class III malocclusion with CLP (n = 68) and without CLP (n = 68). MAIN OUTCOME MEASURES: QOL and OHRQOL were assessed using the World Health Organization Quality of Life-BREF (WHOQOL-BREF) questionnaire and the Oral Health Impact Profile-14 questionnaire, respectively. TMDs and psychological factors were assessed using the Research Diagnostic Criteria for TMD (RDC/TMD). RESULTS: No differences in QOL were found between the groups (P > 0.05). Patients with CLP reported a better OHRQOL (P = 0.025) in the physical pain, physical disability, and psychological disability domains (P < 0.05). Patients with CLP presented with less myofascial pain (OR, 0.28; 95% CI, 0.11-0.71] and other articular conditions (OR 0.24; 95% CI 0.06-0.90]. More patients with CLP reported no chronic pain (P = 0.012). The QOL of patients with CLP with no depression or with no nonspecific physical symptoms including pain (NSPSIP) was better than that of patients without CLP. The OHRQOL of patients with CLP without TMDs or no psychological factors was better than that of patients without CLP. CONCLUSIONS: Patients with skeletal Class III malocclusion who require orthognathic surgery with CLP have better OHRQOL and present with fewer TMDs than those patients without CLP.

Oral Cleft Related-Genes may be Involved in Root Curvature of Maxillary Lateral Incisors.

The maxilla is formed by the medial nasal and maxillary processes fusion. The dental lamina develops from 2 origins connecting in the lateral incisor. The maxillary lateral incisor region is often affected by dental anomalies and clefting. It is possible that genes involved in oral cleft could also be associated with a variety of phenotypic variations in the maxillary lateral incisor. In this phenotype-genotype study, we explored the association between polymorphisms in the oral-cleft-related genes BMP2 and BMP4 and root curvature of maxillary lateral incisors.Cross-sectional study.Universities and private clinics.Panoramic radiographs and DNA from 231 patients were analyzed.Schneider method (1971) was applied to estimate the degree of root curvature of the maxillary lateral incisors and to classify the root as straight (5° or less) or curved (higher than 5°). Genetic polymorphisms in BMP2 (rs235768 and rs1005464) and BMP4 (rs17563) were genotyped. Statistical analysis was performed.A total of 401 teeth (199 left and 202 right) were evaluated. Genetic analysis demonstrated trends toward association for the rs1005464 in BMP2 (P = .025) in co-dominant model and in dominant model (P = .026) for left incisors. The rs235768 in BMP2 showed trends toward association with the degree of root curvature in left incisors in the recessive model (P = .031). rs17563 in BMP4 also showed trends toward association with the degree of the root curvature in left incisors (P = .019).BMP2 (rs235768 and rs1005464) and BMP4 (rs17563) might be involved in maxillary lateral incisor root curvature.

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.

Orthognathic surgery in class II patients: a longitudinal study on quality of life, TMD, and psychological aspects.

OBJECTIVES: To evaluate, longitudinally, the impacts of orthognathic surgery in patients with skeletal class II malocclusion on oral health-related quality of life (OHRQoL), temporomandibular disorders (TMD) and psychological symptoms. MATERIALS AND METHODS: Forty-three patients with skeletal class II malocclusion who were submitted to orthognathic surgery were evaluated during their preoperative and postoperative periods. They answered the short version of the Oral Health Impact Profile (OHIP-14) and were also diagnosed according to Axes I and II of the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). The evolution of OHRQoL and TMD before and after surgery was verified, and the relationships among these variables were found through statistical analysis using Wilcoxon, McNemar, chi-square, and Mann-Whitney tests, with a 5% significance level. RESULTS: The median of the overall OHIP-14 score and five domains decreased after orthognathic surgery (p < 0.05), the functional limitation domain increased (p = 0.014), and the physical disability domain did not show an association (p = 0.133). There were improvements in articular pain (p = 0.016), chronic pain (p = 0.019), and nonspecific physical symptoms excluding pain (p = 0.013). In addition, an association was found between poorer OHRQoL (overall scale and domains) and the Axis II variables of the RDC/TMD (p < 0.05). CONCLUSION: Orthognathic surgery improved perceived OHRQoL, articular pain, and chronic pain. The conditions of Axis II of the RDC/TMD interfered with OHRQoL postoperatively. CLINICAL RELEVANCE: Although orthognathic surgery improves QoL and some TMD conditions in skeletal class II patients, poorer postoperative outcomes are observed when psychological conditions are present.

Odontogenesis-related candidate genes involved in variations of permanent teeth size.

OBJECTIVE: The aim of the study was to evaluate the association between genetic polymorphisms in RUNX2, BMP4, BMP2, TGFß1, EGF, and SMAD6 and variations in permanent tooth size (TS). MATERIALS AND METHODS: This cross-sectional study evaluated 110 individuals' dental casts to determine the maximum tooth crown size of all fully erupted permanent teeth (third molars were excluded) in the mesiodistal (MD) and buccolingual (BL) dimensions. Genomic DNA was obtained from the epithelial cells of the oral mucosa to evaluate the genetic polymorphisms in RUNX2 (rs59983488 and rs1200425), BMP4 (rs17563), BMP2 (rs235768 and rs1005464), TGFß1 (rs1800470), EGF (rs4444903), and SMAD6 (rs2119261 and rs3934908) through real-time PCR. The data were submitted to statistical analysis with a significance level of 0.05. RESULTS: The genetic polymorphisms rs59983488, rs1200425, rs17563, rs235768, rs1005464, rs1800470, and rs4444903 were associated with MD and BL TS of the upper and lower arches (p < 0.05). The polymorphism rs2119261 was associated with variation in TS only in the upper arch (p < 0.05). The rs3934908 was not associated with any TS measurement (p > 0.05). CONCLUSIONS: In summary, this study reports novel associations between variation in permanent TS and genetic polymorphisms in RUNX2, BMP4, BMP2, TGFß1, EGF, and SMAD6 indicating a possible role of these genes in dental morphology. CLINICAL RELEVANCE: Polymorphisms in odontogenesis-related genes may be involved in dental morphology enabling a prediction of permanent TS variability. The knowledge regarding genes involved in TS might impact the personalized dental treatment, considering that patients' genetic profile would soon be introduced into clinical practice to improve patient management.

Genetic variants in tooth agenesis-related genes might be also involved in tooth size variations.

OBJECTIVE: The present study aimed to evaluate if genetic variants in PAX9, MSX1, TGFα, FGF3, FGF10, FGF13, GLI2 and GLI3 are involved in TS of permanent teeth. MATERIALS AND METHODS: Pretreatment dental records from orthodontic patients were assessed prior to recruitment. Patients with tooth agenesis and congenital anomalies (including oral cleft) and/or syndromes were excluded. Dental casts were used to measure the maximum crown dimensions of all fully erupted permanent teeth except second and third molars in mesiodistal direction. Teeth with caries, occlusal wear, mesiodistal restorations, and obvious deformities were not evaluated. Genomic DNA samples were used for genotyping. The allelic discrimination of 13 genetic variants was performed. The associations between TS and genotype were analyzed by linear regression, adjusted by gender at a significance level of p ≤ 0.05. RESULTS: Genetic polymorphisms in the tooth agenesis-related genes studied here were associated with increased and decreased TS, in both maxilla and mandible (p < 0.05). CONCLUSION: This study reported associations of novel tooth agenesis-related gene variants with permanent tooth size variations. CLINICAL RELEVANCE: The presence of some genetic variants could allow the prediction of permanent tooth size.

The role of 25-hydroxyvitamin-D3 and vitamin D receptor gene in human periodontal ligament fibroblasts as response to orthodontic compressive strain: an in vitro study.

BACKGROUND: This study aimed to investigate, if different physiological concentrations of vitamin D (25(OH)D3) and single nucleotide polymorphisms in vitamin D receptor (VDR) gene have an impact on gene expression in human periodontal ligament (hPDL) fibroblasts induced by simulated orthodontic compressive strain. METHODS: A pool of hPDL fibroblasts was treated in absence or presence of 25(OH)D3 in 3 different concentrations (10, 40 and 60 ng/ml). In order to evaluate the role of single nucleotide polymorphisms in the VDR gene, hPDL fibroblasts from 9 patients were used and treated in absence or presence of 40 ng/ml 25(OH)D3. Each experiment was performed with and without simulated orthodontic compressive strain. Real-time PCR was used for gene expression and allelic discrimination analysis. Relative expression of dehydrocholesterol reductase (DHCR7), Sec23 homolog A, amidohydrolase domain containing 1 (AMDHD1), vitamin D 25-hydroxylase (CYP2R1), Hydroxyvitamin D-1-α hydroxylase, receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), cyclooxygenase-2 (COX-2) and interleukin-6 (IL6) was assessed. Three single nucleotide polymorphisms in VDR were genotyped. Parametric or non-parametric tests were used with an alpha of 5%. RESULTS: RANKL, RANKL:OPG ratio, COX-2, IL-6, DHCR7, CYP2R1 and AMDHD1 were differentially expressed during simulated orthodontic compressive strain (p < 0.05). The RANKL:OPG ratio was downregulated by all concentrations (10 ng/ml, 40 ng/ml and 60 ng/ml) of 25(OH)D3 (mean = 0.96 ± 0.68, mean = 1.61 ± 0.66 and mean = 1.86 ± 0.78, respectively) in comparison to the control (mean 2.58 ± 1.16) (p < 0.05). CYP2R1 gene expression was statistically modulated by the different 25(OH)D3 concentrations applied (p = 0.008). Samples from individuals carrying the GG genotype in rs739837 presented lower VDR mRNA expression and samples from individuals carrying the CC genotype in rs7975232 presented higher VDR mRNA expression (p < 0.05). CONCLUSIONS: Simulated orthodontic compressive strain and physiological concentrations of 25(OH)D3 seem to regulate the expression of orthodontic tooth movement and vitamin-D-related genes in periodontal ligament fibroblasts in the context of orthodontic compressive strain. Our study also suggests that single nucleotide polymorphisms in the VDR gene regulate VDR expression in periodontal ligament fibroblasts in the context of orthodontic compressive strain.

Human permanent tooth sizes are associated with genes encoding oestrogen receptors.

OBJECTIVE: To evaluate if genetic polymorphisms in the oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2) genes encoded for oestrogen receptors alpha (ERα) and beta (ERß) are involved in permanent tooth size. DESIGN: Cross-sectional study. SETTING: Orthodontic Clinic at School of Dentistry of Ribeirão Preto, University of São Paulo. PARTICIPANTS: A total of 108 orthodontic patients. MATERIALS AND METHODS: Pre-treatment orthodontic records were evaluated. Dental casts were used to determine the maximum crown measurements of fully erupted permanent teeth in the mesiodistal dimensions. Second and third molars were not included in the analysis. Genomic DNA samples were used for the genotyping of four genetic polymorphisms: ESR1 (rs9340799 and rs2234693) and ESR2 (rs1256049 and rs4986938). The associations between tooth size and sex were evaluated using t test. The associations between tooth size and genotype were analysed with linear regression and adjusted by sex at an alpha of P⩽0.05. RESULTS: Female patients presented smaller tooth size than male patients. A statistically significant difference was observed in almost all teeth (P<0.05). The genetic polymorphisms in rs9340799, rs2234693, rs1256049 and rs4986938 were associated with some tooth sizes in both the maxilla and mandible (P<0.05). CONCLUSION: This study provides evidence that genetic polymorphisms in ESR1 and ESR2 could be associated with tooth size in permanent teeth.

Depression, temporomandibular disorders, and genetic polymorphisms in IL6 impact on oral health-related quality of life in patients requiring orthognathic surgery.

PURPOSE: To assess oral health-related quality of life (OHRQoL) in patients requiring orthognathic surgery, and evaluate if depression, temporomandibular disorders (TMD), and genetic polymorphisms in interleukin-6 (IL6) influence their OHRQoL. METHODS: A total of 132 individuals included in three different groups. Two groups were composed by patients with dentofacial deformity (DFD) Class II (n = 44) or Class III (n = 44) malocclusions, requiring orthognathic surgery. The control group (n = 44) included individuals without DFD. Patients from all groups were evaluated in preoperative appointments to assessOHRQoL, TMD, and genetic polymorphisms in IL6. OHRQoL was assessed using the 14-item Oral Health Impact Profile (OHIP-14). TMD and depression were assessed using Research Diagnostic Criteria for Temporomandibular Disorders protocol. The genetic polymorphisms rs1800795 and rs1800796 in IL6 were assessed through genomic DNA using real-time polymerase chain reaction. RESULTS: OHIP-14 scores were increased in patients with depression, myofascial pain, and inflammatory temporomandibular joint alterations in the right side, regardless of sex and DFD group. Individual homozygous CC in rs1800795 had increased values in domains "social disability" and "handicap" of the OHIP-14 compared with those who were homozygous GG. Individual heterozygous CG in the rs1800796 demonstrated increased values in domain "psychological discomfort" compared with those homozygous for CC and GG. CONCLUSION: In individuals requiring orthognathic surgery, depression, TMD, and genetic polymorphisms in IL6 contribute to negative impact on OHRQoL. These physical and emotional conditions, together with biological pathways, should receive more attention in treatment plans, in order to improve the patients' quality of life.

Evaluation of Tissue Tensions in Segmental Maxillary Osteotomies by Finite Element Analysis.

PURPOSE: Maxillary segmentation associated with Le Fort I osteotomy is a surgical technique used to correct transverse maxillary discrepancies. Notwithstanding advances over the years, there are still complications arising from this surgical intervention, including the maintenance of sufficient blood supply and excessive tension of the palatal fibromucosa. Therefore, the aim of this study was to analyze the effect of the force applied during surgery on bone dislocation and fibromucosa tension in different maxillary segmentation designs by finite element analysis. METHODS: A 3-dimensional skull was generated from tomographic images. We worked with 4 models. In 2 models, we divided the maxilla into 3 segments: one with osteotomy between the lateral incisor and canine and the other between the canine and first premolar. In the other 2 models, we divided the maxilla into 4 segments with the same osteotomies previously mentioned. A force of 100 N was applied to the palatal surfaces of the right and left permanent maxillary first molars. RESULTS: When comparing the technique between 3 and 4 segments with the same interdental osteotomy, we evidenced greater bone dislocation and less fibromucosa tension in the 3-segment technique. When we contrast the same number of segments with different regions of interdental osteotomy, we noticed a lower fibromucosa tension and a greater bone dislocation in the lateral incisors and canine. CONCLUSIONS: The technique with 3 segments and with interdental osteotomy between the lateral incisor and canine presented less resistance, allowing greater dislocation and consequently generating less mucosa tension.

The relationship between molar incisor hypomineralization, dental caries, socioeconomic factors, and polymorphisms in the vitamin D receptor gene: a population-based study.

OBJECTIVES: The purpose of this cross-sectional study was to investigate whether polymorphisms in vitamin D receptor (VDR) genes increase the prevalence of dental caries, molar incisor hypomineralization (MIH), and hypomineralized primary second molars (HPSM). MATERIAL AND METHODS: A representative population-based sample of 731 schoolchildren, 8 years of age, was randomly selected in Curitiba, Paraná, Brazil. MIH, HPSM, and dental caries were clinically assessed by four calibrated examiners (kappa > 0.80) using European Academy of Pediatric Dentistry (2003) criteria, the modified Developmental Defects of Enamel (DDE) index, and the Decayed, Missing, or Filled Teeth (DMFT) index by the World Health Organization (2013), respectively. The VDR rs739837 and rs2228570 polymorphisms were genotyped using real-time polymerase chain reaction. Associations were analyzed by Poisson regression with robust variance (α = 0.05). RESULTS: Schoolchildren with MIH presented a higher prevalence of dental caries (DMFT > 1, PR = 2.52, confidence interval = 1.60-3.97, p ≤ 0.001). No association was observed between MIH, HPSM, and dental caries, with rs739837 and rs2228570 polymorphisms. Individuals with the GT/GG genotype in rs739837 polymorphism presented a higher prevalence of MIH in molars and incisors than individuals TT (PR = 2.34, confidence interval = 1.08-5.07, p = 0.03). CONCLUSION: Children with MIH presented a significant higher prevalence of dental caries than children without MIH. To carry at least one G allele in rs739837 was associated to higher prevalence of MIH in molars and incisors. CLINICAL RELEVANCE: Our findings suggested that more severe cases with incisors affected by MIH could be associated with polymorphism in VDR gene.