Evidence of Association between MTRR and TNF-α Gene Polymorphisms and Oral Health-Related Quality of Life in Children with Anterior Open Bite.

Genetic polymorphisms could explain the inter-individual differences in the oral health-related quality of life (OHRQoL) of children with anterior open bite (AOB). OBJECTIVE: To assess the impact of AOB on OHRQoL in children and to evaluate whether MTR (rs1805087), MTRR (rs1801394), TGFß1 (rs1800469) and TNF-α (rs1799964, rs1799724 and rs1800629) genes are potential biomarkers for OHRQoL in children with AOB. STUDY DESIGN: A cross-sectional study was performed with 173 children aged between 2-6 years. The Brazilian version of Early Childhood Oral Health Impact Scale (ECOHIS) was applied. Genetic polymorphisms were analyzed using real-time PCR. Mann-Whitney U-test and Chi-square were used. RESULTS: The overall mean ECOHIS scores were 5.49 (SD= 5.72) and 3.45 (SD = 4.49) (p < 0.01) in the AOB and control groups, respectively. Children with the CC genotype of TNF-α (rs1799724) had a significantly higher psychological QoL level. The MTRR AA genotype group showed a lower QoL level in the child subscale (p = 0.006), function (p = 0.017), and psychological (p = 0.006) domains. There was no significant difference between OHRQoL and the genetic polymorphisms in MTR and TGFß1. CONCLUSIONS: Genetic polymorphisms in TNF-α and MTRR are associated with the impact on the OHRQoL in children with AOB.

Association between craniofacial morphological patterns and tooth agenesis-related genes.

BACKGROUND: The aim of the present study was to assess if genetic polymorphisms in tooth agenesis (TA)-related genes are associated with craniofacial morphological patterns. METHODS: This cross-sectional, multi-center, genetic study evaluated 594 orthodontic Brazilians patients. The presence or absence of TA was determined by analysis of panoramic radiography. The patients were classified according to their skeletal malocclusion and facial growth pattern by means of digital cephalometric analysis. Genomic DNA was extracted from squamous epithelial cells of buccal mucosa and genetic polymorphisms in MSX1 (rs1042484), PAX9 (rs8004560), TGF-α (rs2902345), FGF3 (rs1893047), FGF10 (rs900379), and FGF13 (rs12838463, rs5931572, and rs5974804) were genotyped by polymerase chain reaction using TaqMan chemistry and end-point analysis. RESULTS: Genotypes (p = 0.038) and allele (p = 0.037) distributions for the FGF3 rs1893047 were significantly different according to the skeletal malocclusion. Carrying at least one G allele increased in more than two times the chance of presenting skeletal class III malocclusion (OR = 2.21, CI 95% = 1.14-4.32; p = 0.017). There was no association between another skeletal craniofacial pattern and some polymorphism assessed in the present study. CONCLUSION: Our results suggest that the genetic polymorphism rs1893047 in FGF3 might contribute to variations in the craniofacial sagittal pattern.

Tooth agenesis-related GLI2 and GLI3 genes may contribute to craniofacial skeletal morphology in humans.

OBJECTIVE: The present cross-sectional, multi-centre, genetic study aimed to determine, whether single nucleotide polymorphisms (SNPs) in tooth agenesis (TA)-associated GLI2 and GLI3 genes contribute to the development of craniofacial skeletal morphology in humans. DESIGN: Orthodontic patients from an ethnically heterogeneous population were selected for the present study (n = 594). The presence or absence of TA was determined by analysis of panoramic radiography and dental records. The subjects were classified according to their skeletal malocclusion and facial growth pattern by means of digital cephalometric analysis. Genomic DNA was extracted from squamous epithelial cells of the buccal mucosa and SNPs in GLI2 (rs3738880, rs2278741) and GLI3 (rs929387, rs846266) were analysed by polymerase chain reaction using TaqMan chemistry and end-point analysis. RESULTS: Class II skeletal malocclusion presented a significantly lower frequency of TA (P < 0.05). Subjects without TA showed significantly higher ANB angles (P < 0.05). Genotype and/or allele distributions of the SNPs in GLI2 (rs3738880, rs2278741) and GLI3 (rs846266) were associated with the presence of TA (P < 0.05). The SNPs rs3738880, rs2278741 and rs929387 were also associated with some type of skeletal malocclusion (P < 0.05), but not with the facial growth pattern (P > 0.05). The G allele for TA-related GLI2 rs3738880 was strongly linked to the presence of Class III skeletal malocclusion (OR = 2.03; 95% CI = 1.37-3.03; P<3125 × 10-6). GLI2 rs2278741 C allele was overrepresented in individuals without TA, suggesting it as a protective factor for this dental phenotype (OR = 0.43; 95% CI = 0.24-0.78; P<625 × 10-5). CONCLUSION: The present study suggests that SNPs in TA-associated GLI2 and GLI3 genes may also play a role in the development of skeletal malocclusions. rs3738880 and rs2278741 in GLI2 seems to contribute to the genetic background for skeletal Class III and TA, respectively. TA could be an additional predictor of craniofacial morphology in some cases. Further research replicating the reported associations should be performed.

Determination of TNF-a Gene Polymorphisms on Skeletal Pattern in Class II Malocclusion.

Bone development and growth is a non-going, life-long process, varying greatly among individuals and much of this variation could be modulated by genetic factors. The purpose of this study was to evaluate the association between the polymorphisms in the TNF-a gene and skeletal class II malocclusion. Single nucleotide polymorphisms in TNF-a (rs1799724; rs1800629) gene were studied in 79 skeletal class II malocclusion and 102 skeletal class I malocclusion subjects from Straight Wire Group of Studies on Orthodontics and Functional Orthopedics for Maxillary from Rio de Janeiro, Brazil. The Genotyping of these selected polymorphisms was carried out by TaqMan real-time PCR using genomic DNA extracted from buccal cells. All allele and genotype frequencies were compared between the groups using the PLINK® software in a free, in a dominant and in a recessive model using a chi-square test (p≤0.05). There was no significant association of TNF-a (rs1799724; rs1800629) genotype and allele distribution with skeletal class II malocclusion. Regardless of the dominant or recessive genetic model, the preferential genotype associations for rs1799724 and rs1800629 was insignificant. In conclusion, no evidence of association is apparent between genetic polymorphisms involving TNF-a and skeletal class II malocclusion or the position of the maxilla and mandible in the postero-anterior direction.

Determination of tnf-a gene polymorphisms on skeletal pattern in class ii malocclusion

Abstract Bone development and growth is a non-going, life-long process, varying greatly among individuals and much of this variation could be modulated by genetic factors. The purpose of this study was to evaluate the association between the polymorphisms in the TNF-a gene and skeletal class II malocclusion. Single nucleotide polymorphisms in TNF-a (rs1799724; rs1800629) gene were studied in 79 skeletal class II malocclusion and 102 skeletal class I malocclusion subjects from Straight Wire Group of Studies on Orthodontics and Functional Orthopedics for Maxillary from Rio de Janeiro, Brazil. The Genotyping of these selected polymorphisms was carried out by TaqMan real-time PCR using genomic DNA extracted from buccal cells. All allele and genotype frequencies were compared between the groups using the PLINK® software in a free, in a dominant and in a recessive model using a chi-square test (p≤0.05). There was no significant association of TNF-a (rs1799724; rs1800629) genotype and allele distribution with skeletal class II malocclusion. Regardless of the dominant or recessive genetic model, the preferential genotype associations for rs1799724 and rs1800629 was insignificant. In conclusion, no evidence of association is apparent between genetic polymorphisms involving TNF-a and skeletal class II malocclusion or the position of the maxilla and mandible in the postero-anterior direction.

Resumo O desenvolvimento e crescimento ósseo é um processo contínuo, que dura toda a vida, variando muito entre os indivíduos e grande parte dessa variação pode ser modulada por fatores genéticos. O objetivo deste estudo foi avaliar a associação entre os polimorfismos no gene TNF-a e a má oclusão da classe II esquelética. Polimorfismos no gene TNF-a (rs1799724; rs1800629) foram estudados em 79 indivíduos com má oclusão esquelética de classe II e 102 indivíduos com má oclusão esquelética classe I do Grupo de Estudos em Ortodontia e Ortopedia Funcional dos Maxilares do Rio de Janeiro, Brasil. A genotipagem destes polimorfismos foi realizada por PCR em tempo real, através de DNA genômico extraído de células bucais. Todas as frequências alélicas e genotípicas foram comparadas entre os grupos utilizando o software PLINK® em um modelo livre, dominante e recessivo. Foi aplicado o teste do qui-quadrado (p≤0,05). Não houve associação significativa na distribuição genotipica e alélica do gene TNF-a (rs1799724; rs1800629) com a má oclusão de classe II esquelética. Independentemente do modelo genético dominante ou recessivo, as associações genotípicas preferenciais para rs1799724 e rs1800629 foram insignificantes. Pode-se concluir que, não existe evidência de associação entre polimorfismos genéticos envolvendo TNF-a e má oclusão esquelética de classe II ou a posição da maxila e mandíbula na direção póstero-anterior.

Genetic variants in ACTN3 and MYO1H are associated with sagittal and vertical craniofacial skeletal patterns.

OBJECTIVE: This study aimed to evaluate the association of genetic variants inACTN3 and MYO1H with craniofacial skeletal patterns in Brazilians. DESIGN: This cross-sectional study enrolled orthodontic and orthognathic patients selected from 4 regions of Brazil. Lateral cephalograms were used and digital cephalometric tracings and analyzes were performed for craniofacial phenotype determination. Participants were classified according to the skeletal malocclusion in Class I, II or III; and according to the facial type in Mesofacial, Dolichofacial or Brachyfacial. Genomic DNA was extracted from saliva samples containing exfoliated buccal epithelial cells and analyzed for genetic variants inACTN3 (rs678397 and rs1815739) and MYO1H (rs10850110) by real-time PCR. Chi-square or Fisher's exact tests were used for statistical analysis (α = 5%). RESULTS: A total of 646 patients were included in the present study. There was statistically significant association of the genotypes and/or alleles distributions with the skeletal malocclusion (sagittal skeletal pattern) and facial type (vertical pattern) for the variants assessed inACTN3 (P < 0.05). For the genetic variant evaluated in MYO1H, there was statistically significant difference between the genotypes frequencies for skeletal Class I and Class II (P < 0.05). The reported associations were different depending on the region evaluated. CONCLUSION: ACTN3 and MYO1H are associated with sagittal and vertical craniofacial skeletal patterns in Brazilian populations.

Genetic Polymorphism in MMP9 May Be Associated With Anterior Open Bite in Children

Abstract Anterior open bite (AOB) has a multifactorial etiology caused by the interaction of sucking habits and genetic factors. The aim of this study was to evaluate the association between AOB and polymorphisms in genes that encode Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Four hundred and seventy-two children that presented at least one sucking habit were evaluated. Children were examined clinically for the presence of AOB. Genomic DNA was extracted from saliva. Genotyping of the selected polymorphisms in MMP2, MMP3, MMP9, TIMP1 and TIMP2 was carried out by real-time PCR using the TaqMan method. Allele and genotype frequencies were compared between the groups with and without AOB using the PLINK® software in a free and in a recessive model using a chi-square test. Logistic regression analysis was implemented (p≤0.05). Two hundred nineteen children had AOB while 253 did not. The polymorphism rs17576 in MMP9 was significantly associated with AOB (p=0.009). In a recessive model GG genotype was a protective factor for AOB (p=0.014; OR 4.6, 95%CI 1.3-16.2). In the logistic regression analysis, none of the genes was associated with AOB. In conclusion, the polymorphism rs17576 (glutamine for arginine substitution) in MMP9 was a protective factor for AOB.

Resumo A mordida aberta anterior apresenta uma etiologia multifatorial causada pela interação entre hábitos de sucção e fatores genéticos. O objetivo deste estudo foi avaliar a associação entre mordida aberta anterior e polimorfismo nos genes que codificam as metaloproteinases da matriz (MMPs) e seus inibidores teciduais (TIMPs). Foram avaliadas 472 crianças que apresentvam pelo menos um hábito de sucção. As crianças foram clinicamente examinadas para avaliar a presença de mordida aberta anterior. DNA genômico foi extraído da saliva. A genotipagem dos polimorfismos selecionados em MMP2, MMP3, MMP9, TIMP1 e TIMP2 foi realizada por PCR em tempo real, usando o método de TaqMan. As frequências alélicas e genotípicas foram comparadas entre os grupos com e sem mordida aberta anterior usando o software PLINK®. Duzentas e dezenove crianças apresentavam mordida aberta anterior enquanto 253 não a apresentavam. O polimorfismo rs17576 em MMP9 estava significativamente associado com mordida aberta anterior (p=0,009). No modelo recessivo (GG versus AG+AA) o genótipo GG foi um fator protetor para mordida aberta anterior (p=0,014; OR 4,6; 95%CI 1,3- 16,2). Concluindo, o polimorfismo rs17576 (substituição de glutamina por arginina) em MMP9 está associado com mordida aberta anterior. Os resultados obtidos suportam a hipótese de que fatores genéticos estão envolvidos com a etiologia da mordida aberta anterior.

Genetic Polymorphism in MMP9 May Be Associated With Anterior Open Bite in Children.

Anterior open bite (AOB) has a multifactorial etiology caused by the interaction of sucking habits and genetic factors. The aim of this study was to evaluate the association between AOB and polymorphisms in genes that encode Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Four hundred and seventy-two children that presented at least one sucking habit were evaluated. Children were examined clinically for the presence of AOB. Genomic DNA was extracted from saliva. Genotyping of the selected polymorphisms in MMP2, MMP3, MMP9, TIMP1 and TIMP2 was carried out by real-time PCR using the TaqMan method. Allele and genotype frequencies were compared between the groups with and without AOB using the PLINK® software in a free and in a recessive model using a chi-square test. Logistic regression analysis was implemented (p≤0.05). Two hundred nineteen children had AOB while 253 did not. The polymorphism rs17576 in MMP9 was significantly associated with AOB (p=0.009). In a recessive model GG genotype was a protective factor for AOB (p=0.014; OR 4.6, 95%CI 1.3-16.2). In the logistic regression analysis, none of the genes was associated with AOB. In conclusion, the polymorphism rs17576 (glutamine for arginine substitution) in MMP9 was a protective factor for AOB.

Avaliação da Relação Causal Entre a Presença de Hábitos Bucais Deletérios, Tipo de Aleitamento e Maloclusões em Crianças na Dentadura Decídua / Causal Relationship between the Oral Habits, Feeding and Malocclusion in Children Deciduous Teeth

As maloclusões, por seu alto índice de prevalência, vêm sendo consideradas um problema de saúde pública. A literatura ressalta a importânciado aleitamento natural para a prevenção de hábitos bucais e maloclusão. O objetivo do estudo foi avaliar a relação das formas de aleitamentocom hábitos bucais deletérios e seu efeito sobre a oclusão na dentição decídua. Um estudo transversal, retrospectivo, foi realizado em 443crianças de 2 a 6 anos de 27 creches públicas de Nova Friburgo, RJ. Os dados foram coletados através de questionários para pais/responsáveis arespeito do tipo de aleitamento e hábitos bucais deletérios. O exame de oclusão foi realizado por 2 examinadores (kappa=0,80). Os dados foramtabulados e analisados, sendo obtida a frequência e a associação das variáveis (Teste qui-quadrado e ODDS Ratio). Foi observado associaçãodo tipo de aleitamento com os seguintes hábitos: sucção de chupeta (OR 0,12 IC 0,05-0,32; p<0,01) e sucção digital (OR 0,35 IC 0,11-1,13;p=0,04), bem como com as seguintes maloclusões: mordida aberta anterior (OR 0,15 IC 0,06-0,41; p<0,01), mordida cruzada posterior (OR0,26 IC 0,05-1,23; p=0,04) e sobressaliência acentuada (OR 0,32 IC 0,09-1,12; p=0,03). Na população estudada, o aleitamento artificial estáassociado ao hábito de sucção de chupeta, sucção digital e maloclusões, destacando-se a mordida aberta anterior, mordida cruzada posterior esobressaliência acentuada. Diante disso é desejável a implementação de programas preventivos de incentivo ao aleitamento natural para essapopulação.

Malocclusions have been considered as a public health problem due to their high prevalence rate. Literature highlights the importance ofbreastfeeding for prevention of oral habits and malocclusion. This study aimed to evaluate the relationship of breastfeeding and harmful oralhabits and effects on deciduous oclusion. A retrospective cross-sectional study was conducted in 443 children aged 2 to 6 years of 27 publickindergartens in Nova Friburgo, RJ. Data were collected through questionnaires to parents/guardians about the type of feeding and oral habits. Occlusal examination was performed by two examiners (kappa=0.80). Data were tabulated and the relationship between the variables was analyzed (chi-square test and odds ratio). It was observed association of type of breastfeeding with the following habits: pacifier sucking (OR 0.12 CI 0.05 to 0.32, p < 0.01 ) and thumb sucking (OR 0.35 CI 0.11 ? 1.13 , p = 0.04) and with the following malocclusions: anterior openbite (OR 0.15 CI 0.06 to 0.41, p < 0.01 ), posterior crossbite (OR 0.26 CI 0.05 to 1.23 , p=0.04 ) and deep overjet (OR 0.32 CI 0.09 to 1.12,p=0.03). In the population studied, artificial breastfeeding is associated with harmful oral habit such as pacifier sucking thumb sucking, andmalocclusions as anterior open bite, posterior crossbite and severe overjet. So, it is desirable to implement preventive programs to encouragebreastfeeding in this population.