Abstract This study aimed to assess whether genetic polymorphisms in MTR and MTRR are potential biomarkers of oral health-related quality of life (OHRQoL) in children with caries. A cross-sectional study was designed wherein pairs of parents/caregivers and children (aged two–five years) were selected. Clinical examination was used to detect dental caries, which were classified as low-severity and high-severity caries. The Early Childhood Oral Health Impact Scale (ECOHIS) questionnaire was used to assess OHRQoL. Genomic DNA extracted from the saliva was used to analyze two missense genetic polymorphisms: MTR (rs1805087) and MTRR (rs1801394). Mann–Whitney non-parametric test was used to analyze candidate genes with OHRQoL scale and domain, with a significance level of p≤0.05. MTR (rs1805087) was found associated (p = 0.05) with children’s OHRQoL subscale scores in the dominant model (GG + AG). Genetic polymorphisms in MTR may increase the risk of poor OHRQoL in children with caries. Further studies are needed to investigate genetics, molecular factors, and OHRQoL.

Abstract An increasing number of systematic reviews (SR) has investigated the association between dental caries and nutritional status in children and adolescents, thus requiring an overview to compile the information in a single piece of evidence. Therefore, this study aimed to evaluate and summarize evidence from published SR on the association between dental caries and nutritional status in children and adolescents. A wide search was conducted on May 29, 2023, in six databases (Medline via PubMed, Scopus, Web of Science, Cochrane library, Embase, and the Virtual Health Library – VHL). An additional search was performed in the gray literature (Open grey and Google Scholar), SR registration databases, and the list of references of the included SR. Our inclusion criteria were based on acronym PECOS. Overall, two reviewers independently extracted the data, evaluated the risk of bias (ROBIS), and assessed the quality of the chosen studies (AMSTAR-2). Data from the included meta-analysis were summarized and certainty of evidence using the GRADE approach was performed. After removing duplicates and applying our eligibility criteria, 19 SR from 2006-2022 were included. We found that 17 SR showed high risk of bias and critically low methodological quality. We observed an association between dental caries experiences and nutritional status since seven SR found an association between obesity/overweight and dental caries; one, an association between underweight and dental caries; and eleven, no associations. The meta-analysis showed divergent results according to the study designs, used indices, and participants’ age group, and were scored as having a very low certainty of evidence. Therefore, based on the high risk of bias, low methodological quality, and very low certainty of evidence of the chosen SR, most studies found no association between children and adolescents’ nutritional status and dental caries experience.

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.

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.

Abstract: This cross-sectional study aimed to assess if genetic polymorphisms in TNF- α are associated with a negative impact on Oral Health-Related Quality of Life (OHRQoL) in children with dental caries. A total of 307 pairs of parents/caregivers and children aged two to five years were selected. The children were clinically evaluated and classified according to caries experience and severity of active caries. The Brazilian Portuguese version of the Early Childhood Oral Health Impact Scale (ECOHIS) was used to assess OHRQoL. Genotyping analysis of genetic polymorphisms in TNF- α (rs1799724, rs1799964, and rs1800629) was performed using real-time polymerase chain reaction. In the recessive model, children with the CC genotype of TNF-α (rs1799964) had a significantly high chance of poor OHRQoL in the symptom domain (pain), in both the caries experience (p = 0.045) and the high-severity active caries phenotypes (p = 0.033) (Mann-Whitney U test). It was concluded that genetic polymorphisms in TNF-α are associated with OHRQoL related to the symptom domain (pain), suggesting that TNF-α could be used as a potential biomarker for OHRQoL. Understanding the genetic aspects associated with OHRQoL will allow the early identification of patients with OHRQoL disparities and provide personalized healthcare.

Resumo Este estudo avaliou a associação entre polimorfismos em genes que codificam os receptores de estrogênio 1 (ESR1) e 2 (ESR2), receptor de vitamina D (VDR) e no microRNA17 (que se liga à ESR1 e VDR) e a periodontite apical persistente (PAP) após o tratamento endodôntico. Foram incluídos 162 pacientes com tratamento endodôntico concluído há pelo menos um ano e que apresentavam periodontite apical no início da terapia endodôntica. Exames clínicos e radiográficos foram realizados para avaliar a presença de PAP ou tecidos perirradiculares saudáveis (cicatrizados). As amostras de saliva foram coletadas como fonte de DNA genômico. A genotipagem de ESR1 (rs2234693 e rs9340799), ESR2 (rs1256049 e rs4986938), VDR (rs739837 e rs2228570) e miRNA17 (rs4284505) foram realizadas por PCR em tempo real. O teste do qui-quadrado foi utilizado para a distribuição das frequências genotípicas e alélicas. A análise de haplótipos também foi realizada. Oitenta e nove pacientes foram incluídos no grupo “curado” e 73 no grupo “PAP”. Não foi encontrada associação entre os polimorfismos alélicos e genotípicos estudados e a PAP (p>0,05). Concluí-se que os polimorfismos genéticos em ESR1, ESR2, VDR e miRNA17 não estão associados à PAP.

Abstract This study evaluated the association between polymorphisms in genes encoding estrogen receptors 1 (ESR1) and 2 (ESR2), vitamin D receptor (VDR) and in microRNA17 (which binds to ESR1 and VDR) with persistent apical periodontitis (PAP) after the endodontic treatment. We included 162 patients who completed endodontic treatment at least one year ago and presented apical periodontitis at the beginning of the root canal therapy. Clinical and radiographic exams were performed to evaluate the presence of PAP or healthy periradicular tissues (healed). Saliva samples were collected as a genomic DNA. The genotyping of ESR1 (rs2234693 and rs9340799), ESR2 (rs1256049 and rs4986938), VDR (rs739837 and rs2228570) and miRNA17 (rs4284505) were performed by real-time PCR. Chi-square test was used to the distribution of genotype and allele frequencies. Haplotype analysis was also performed. Eighty-nine patients were included in the “healed” group and 73 in the “PAP” group. No association was found between the allelic and genotypic polymorphisms studied and PAP (p>0.05). Haplotype analysis also did not demonstrated an association (p>0.05). In conclusion, the genetic polymorphisms in ESR1, ESR2, VDR and miRNA17 are not associated with PAP.

Abstract This study was performed to evaluate the interplay between dental caries, nutritional status, and genetic polymorphisms in TAS1R1 and TAS1R2 (taste receptor, type 1, member 1 and 2) in preschool children and pre-adolescents. We included 525 subjects (306 preschool children and 219 pre-adolescents). Parents/caregivers answered a self-administered questionnaire about their children’s systemic health, characteristics, oral hygiene habits, and diet. Clinical examination was performed to evaluate dental caries and nutritional status. Saliva samples were collected for DNA extraction. The genotyping of rs17492553 ( TAS1R1 ), rs3935570, and rs4920566 ( TAS1R2 ) polymorphisms was performed using real-time PCR with Taqman Genotyping Master Mix and SNP assay. Both univariate and multivariate Poisson regression analyses with robust variance were used for the data analysis. In preschool children, consumption of sweets between meals increased the prevalence of dental caries by 85% (PR c = 1.85; 95%CI 1.39–2.46; p < 0.001), whereas in pre-adolescents, this prevalence increased by 34% (PR a = 1.34; 95%CI 1.11–1.62; p = 0.002), regardless of genetic polymorphisms . Moreover, individuals carrying at least one allele C in rs17492553 presented 23% more prevalence of dental caries (PR a = 1.23; 95%CI 1.02–1.49 p = 0.030). Nutritional status was not associated with dental caries, neither with genetic polymorphisms . Consumption of sweets between meals increased the prevalence of dental caries. In pre-adolescents, rs17492553 genetic polymorphism in TAS1R1 was associated with dental caries.

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.

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.

Introdução: Os traumatismos dentários (TD) constituem um problema de saúde pública. Objetivo: O objetivo deste estudo foi detectar o impacto do TD na qualidade de vida relacionada à saúde bucal (QVRSB) de crianças e seus familiares assistidos em Programa de Atendimento ao Traumatismo Dentário (PATD) e avaliar a propriedade psicométrica de um instrumento de QVRSB nessa população. Método: Um estudo do tipo transversal incluindo uma amostra não probabilística de crianças de 2 6 anos de um período de 5 anos de coleta foi realizado. Utilizouse a classificação de Andreasen para avaliar os TD e a versão brasileira do Early Childhood Oral Health Impact Scale (ECOHIS) para detectar o impacto sobre a QVRSB. Baseado no teste de Kolmogorov-Smirnov, o teste t Student foi aplicado para comparar as médias de impacto nos casos de TD complicados e não complicados considerando p < 0,05. Resultados: A amostra final contou com 146 crianças (média de idade de 4,31 ± 1,68). A busca por tratamento foi mediada em 90% dos casos e 56,7% dos TD ocorreram em tecido de suporte. O ECOHIS apresentou propriedades satisfatórias na população empregada (± de Cronbach = 0,83 e teste-reteste/ICC = 0,79). A média do ECOHIS foi 6,79 ± 8,64 na escala total, 4,29 ± 6,46 na subescala criança e 2,50 ± 3,06 na subescala família. Os TD complicados apresentaram maiores escores na escala total (p = 0,036), subescala criança (p = 0,038), domínio sintoma (p = 0,049), domínio função (p = 0,030). Conclusões: O instrumento utilizado foi satisfatório e pode detectar que os TD complicados geraram impacto negativo na QVRSB de crianças e sua família.

Background: Traumatic dental injury (TDI) constitutes a public health problem. - Objective: The objective of this study was to detect the impact of TDI on oral health-related quality of life (OHRQoL) of preschool children in a dental trauma care program and to evaluate the psychometric properties of the OHRQoL instrument in this population. - Methods: A cross-sectional study including a nonprobabilistic sample of 2- to 6-year-old children from a 5-year collection period was performed. We used Andreasen s classification to evaluate TDI and the Brazilian version of the Early Childhood Oral Health Impact Scale (ECOHIS) to assess OHRQoL. Based on the Kolmogorov-Smirnov test, Student s t test was applied to compare the means of impact in the cases of complicated and uncomplicated TDI considering a p value <0.05. - Results: The final sample was composed of 146 children (mean age 4.31 ± 1.68 years). The search for treatment was 90% mediated and 56.7% TDI was in support of tissue. The ECOHIS had satisfactory properties (Cronbach s ± = 0.83 and test-retest/intraclass correlation coefficient = 0.79). The ECOHIS mean was 6.79 ± 8.64 for the total scale, 4.29 ± 6.46 for the child subscale, and 2.50 ± 3.06 for the family subscale. Complicated TDI had a greater impact on OHRQoL in total score ( p = 0.036), child subscale ( p = 0.038), symptoms domain ( p = 0.049), and function domain ( p = 0.030). - Conclusions: The OHRQoL instrument was satisfactory. It was detected that complicated TDI impacts negatively on the OHRQoL of children and their families.

Resumo A periodontite apical persistente (PAP) é uma condição que envolve uma resposta inflamatória e imunológica causada principalmente por infecções polimicrobianas de origem anaeróbia no sistema de canais radiculares, tornando o resultado e o acompanhamento do tratamento do canal radicular intimamente relacionados à resposta do hospedeiro. O reparo da periodontite apical pode estar associado a polimorfismos genéticos. Este estudo teve como objetivo avaliar a associação entre os polimorfismos genéticos do HIF1A (rs2301113 e rs2057482) com a PAP em pacientes brasileiros. Indivíduos com pelo menos 1 ano de acompanhamento após o tratamento do canal radicular (TCR) foram agendados para consulta de acompanhamento. Sessenta e quatro indivíduos com sinais/sintomas de PAP e 84 indivíduos com dentes tratados endodonticamente e tecidos perirradiculares saudáveis (cicatrizados) foram incluídos no presente estudo. O DNA genômico foi extraído da saliva e utilizado para a genotipagem do HIF1A por PCR em tempo real. O genótipo e as frequências alélicas foram comparados por teste c2 ou exato de Fisher e odds-ratio foi implementado por meio do software Epi Info 3.5.2. Todos os testes realizados foram estabelecidos com a=0,05. Não houve associação entre alelo e distribuição genotípica para polimorfismos do HIF1A e PAP (p> 0,05). Os polimorfismos genéticos em HIF1A não foram associados à periodontite apical persistente.

Abstract Persistent apical periodontitis (AP) is a situation involving an inflammatory and immune response caused mainly by anaerobic polymicrobial infection of the root canal system and the outcome and follow-up of the root canal treatment has been reported as intimately related to host response. The apical periodontitis repair might be associated with genetic polymorphisms. This study aimed to evaluate the association between HIF1A genetic polymorphisms (rs2301113 and rs2057482) with PAP in Brazilian patients. Subjects with at least 1 year of follow-up after root canal therapy (RCT) were recalled. Sixty-four subjects with signs/symptoms of PAP and 84 subjects with root canal-treated teeth exhibiting healthy perirradicular tissues (healed) were included. Genomic DNA was extracted from saliva and used for HIF1A genotyping by real-time PCR. Genotype and allele frequencies were compared by c2 or Fisher’s exact tests and odds ratio was implemented, using Epi Info 3.5.2. All tests were performed with an established alpha of 0.05. There was no association between allele and genotype distribution for HIF1As polymorphisms and PAP (p>0.05). The genetic polymorphisms in HIF1A were not associated with persistent apical periodontitis.

Resumo A cárie dentária é um problema de saúde pública com impacto na qualidade de vida relacionada à saúde bucal (QVRSB). Este estudo teve como objetivo avaliar a cárie dentária como desfecho em saúde bucal em pré-escolares, por meio da associação de indicadores clínicos e sociodentais que avaliam a QVRSB. Um estudo transversal foi realizado com crianças de 2 a 6 anos de idade que frequentavam creches públicas de um município do sudeste do Brasil. Após o cálculo da amostra, 446 crianças foram selecionadas aleatoriamente por critérios de elegibilidade. A avaliação foi feita por dois profissionais, usando critérios da OMS, que classificaram os sujeitos de acordo com a gravidade de cárie precoce na infância (CPI). Os pais/cuidadores responderam um questionário auto- aplicado de caracterização da amostra e um indicador sociodental (B-ECOHIS). A prevalência de cárie dentária foi de 33,7%. As crianças com alta gravidade de CPI tinha cinco vezes mais chance de sofrer impacto sobre QVRSB. O teste one way ANOVA apresentou associação entre impacto na QVRSB (ECOHIS escores) e CPI. O desfecho cárie em saúde bucal apresentou alta prevalência como indicador clínico e alto impacto sobre a QVRSB como o indicador sociodental. Indicadores clínicos e sociodentais devem ser avaliados em conjunto.

Abstract Dental caries is a public health problem that impacts oral health related to quality of life (OHRQoL). This study aimed to evaluate the outcome of dental caries in children by associating clinical and socio-dental indicators. A cross-sectional study was carried out with 2 to 6-year-old children who attended public day care centers in a city in the Southeast Region of Brazil. After sample calculation, 446 children were randomly selected by eligibility criteria. Two professionals evaluated dental caries using WHO (2013) criteria and classified subjects according to early childhood caries (ECC) severity. Parents/care- givers answered a characterization questionnaire and self-reported socio-dental indicator (B-ECO-HIS). The prevalence of dental caries was 33.7%. The children with high severity of ECC had 5 times higher chance of suffering an impact on OHRQoL. The one way ANOVA test showed that the impact on OHRQoL (ECOHIS scores) was associated with ECC. The outcome dental caries in oral health presented high prevalence as clinical indicator and high impact on OHRQoL as socio dental indicator. Clinical and socio-dental indicators should be evaluated together.

Resumo A cárie dentária é um problema de saúde pública com impacto na qualidade de vida relacionada à saúde bucal (QVRSB). Este estudo teve como objetivo avaliar a cárie dentária como desfecho em saúde bucal em pré-escolares, por meio da associação de indicadores clínicos e sociodentais que avaliam a QVRSB. Um estudo transversal foi realizado com crianças de 2 a 6 anos de idade que frequentavam creches públicas de um município do sudeste do Brasil. Após o cálculo da amostra, 446 crianças foram selecionadas aleatoriamente por critérios de elegibilidade. A avaliação foi feita por dois profissionais, usando critérios da OMS, que classificaram os sujeitos de acordo com a gravidade de cárie precoce na infância (CPI). Os pais/cuidadores responderam um questionário auto- aplicado de caracterização da amostra e um indicador sociodental (B-ECOHIS). A prevalência de cárie dentária foi de 33,7%. As crianças com alta gravidade de CPI tinha cinco vezes mais chance de sofrer impacto sobre QVRSB. O teste one way ANOVA apresentou associação entre impacto na QVRSB (ECOHIS escores) e CPI. O desfecho cárie em saúde bucal apresentou alta prevalência como indicador clínico e alto impacto sobre a QVRSB como o indicador sociodental. Indicadores clínicos e sociodentais devem ser avaliados em conjunto.

Abstract Dental caries is a public health problem that impacts oral health related to quality of life (OHRQoL). This study aimed to evaluate the outcome of dental caries in children by associating clinical and socio-dental indicators. A cross-sectional study was carried out with 2 to 6-year-old children who attended public day care centers in a city in the Southeast Region of Brazil. After sample calculation, 446 children were randomly selected by eligibility criteria. Two professionals evaluated dental caries using WHO (2013) criteria and classified subjects according to early childhood caries (ECC) severity. Parents/care- givers answered a characterization questionnaire and self-reported socio-dental indicator (B-ECO-HIS). The prevalence of dental caries was 33.7%. The children with high severity of ECC had 5 times higher chance of suffering an impact on OHRQoL. The one way ANOVA test showed that the impact on OHRQoL (ECOHIS scores) was associated with ECC. The outcome dental caries in oral health presented high prevalence as clinical indicator and high impact on OHRQoL as socio dental indicator. Clinical and socio-dental indicators should be evaluated together.

Abstract Objectives To evaluate the association between hypoxia during embryo development and oral clefts in an animal model, and to evaluate the association between polymorphisms in the HIF-1A gene with oral clefts in human families. Material and Methods The study with the animal model used zebrafish embryos at 8 hours post-fertilization submitted to 30% and 50% hypoxia for 24 hours. At 5 days post-fertilization, the larvae were fixed. The cartilage structures were stained to evaluate craniofacial phenotypes. The family-based association study included 148 Brazilian nuclear families with oral clefts. The association between the genetic polymorphisms rs2301113 and rs2057482 in HIF-1A with oral clefts was tested. We used real time PCR genotyping approach. ANOVA with Tukey's post-test was used to compare means. The transmission/disequilibrium test was used to analyze the distortion of the inheritance of alleles from parents to their affected offspring. Results For the hypoxic animal model, the anterior portion of the ethmoid plate presented a gap in the anterior edge, forming a cleft. The hypoxia level was associated with the severity of the phenotype (p<0.0001). For the families, there was no under-transmitted allele among the affected progeny (p>0.05). Conclusion Hypoxia is involved in the oral cleft etiology, however, polymorphisms in HIF-1A are not associated with oral clefts in humans.

Abstract: Genetics is an emerging topic in endodontic research focusing on the host response regarding the pathogenesis of apical periodontitis (AP). A number of genetic epidemiological studies carried out by many investigators worldwide have shown evidence of an association between certain candidate genes and AP. Some studies have been conducted on knockout mice with a deficiency in certain proteins, leading to more or less severe AP, and thus suggesting a pivotal role of these genes in AP pathogenesis. Other research has evaluated the association between genetic polymorphisms in humans with different AP aspects; these studies pointed out that genetic polymorphisms in some candidate genes are involved in inter-individual variations in their response to AP. Therefore, the objective of this report was to provide an updated overview of the genes involved in AP pathogenesis, with a focus on the most relevant candidate genes.

Resumo Atualmente as investigações têm focado na identificação de Polimorfismos de Núcleo Único (SNP) envolvidos na resposta do hospedeiro e sua capacidade de gerar uma deficiência de imunidade. O objetivo deste estudo foi realizar uma revisão sistemática (RS) e uma meta-análise para avaliar a associação entre o polimorfismo do gene TNF-α (-308 G> A) e os fenótipos de periodontite apical (PA). Esta RS foi registrada na base de dados PROSPERO, CRD42016035688, e foi conduzida seguindo o método PRISMA. Foi realizada uma ampla pesquisa de estudos. Foram utilizadas as seguintes bases de dados: PubMed, Scopus, Web of Science e BVS (Medline, SciELO, Ibecs e Lilacs). Foram utilizados os seguintes descritores (MeSH) “Periapical Periodontitis,” “Periapical Abscess,” “Polymorphism, Genetic,” and “Polymorphism, Single Nucleotide”. Sinônimos, termos relacionados e termos livres foram incluídos. Foram selecionadas investigações clínicas de indivíduos com diferentes fenótipos de PA em dentes permanentes. Após a aplicação dos critérios de elegibilidade, os estudos selecionados foram classificados através da avaliação da qualidade metodológica. Foi utilizado um modelo de efeito fixo para a metanálise. A pesquisa inicial identificou 71 referências. Após a exclusão de resumos duplicados, 33 foram selecionados. Destes, dois eram elegíveis para a avaliação da qualidade e foram classificados como sendo de evidência moderada. Os estudos incluídos não demonstraram associação entre PA e o TNF-α-308 G>A. No entanto, a metanálise demonstrou associação entre a distribuição do genótipo e os fenótipos da PA (OR = 0,49, intervalo de confiança=0,25, 0,96; p=0,04). O papel do TNF-α-308 G>A em fenótipos da PA é discutível. São necessários mais estudos para confirmar e compreender os mecanismos subjacentes à associação identificada.

Abstract Currently, investigations have focused on the identification of Single Nucleotide Polymorphisms (SNP) involved in host response and its ability to generate an immunity deficiency. The aim of this study was to perform a systematic review (SR) and meta-analysis to evaluate the association between TNF-α -308 G>A polymorphism and apical periodontitis (AP) phenotypes. A broad search for studies was conducted. The following databases were used: PubMed, Scopus, Web of Science, and VHL (Medline, SciELO, Ibecs, and Lilacs). The MeSH terms “Periapical Periodontitis,” “Periapical Abscess,” “Polymorphism, Genetic,” and “Polymorphism, Single Nucleotide” were used. MeSH synonyms, related terms, and free terms were included. Clinical investigations of individuals with different AP phenotypes in permanent teeth were selected. After application of the eligibility criteria, selected studies were qualified by assessing their methodological quality. A fixed effect model was used for the meta-analysis. The initial search identified 71 references. After excluding duplicate abstracts, 33 were selected. From these, two were eligible for quality assessment and were classified as being of moderate evidence. The included studies did not demonstrate association between AP and TNF-α -308 G>A SNP. However, the meta-analysis demonstrated an association between the genotype distribution and AP phenotype (OR= 0.49; confidence interval= 0.25, 0.96; p=0.04). The role of TNF-α -308 G>A SNP in AP phenotypes is debatable. Further studies are needed to confirm and understand the underlying mechanisms of the identified association.

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.

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.