Exploring etiologic contributions to the occurrence of external apical root resorption.

INTRODUCTION: External apical root resorption (EARR) is often an undesirable sequela of orthodontic treatment. Prior studies have suggested a substantial link between EARR and certain genetic components. Single nucleotide polymorphisms (SNPs) may play a role as predisposing factors. This study aimed to investigate the potential association between EARR and various SNPs. METHODS: The study included 218 orthodontic participants of all malocclusions who had available pretreatment and posttreatment panoramic radiographs. The most severely affected maxillary incisor on the radiograph was assessed for EARR using a 0-4 categorical scale. DNA was taken from the saliva samples of the participants, and the SNPs were analyzed using polymerase chain reaction and TaqMan chemistry. Statistical testing was performed to verify any associations with EARR (P <0.05). RESULTS: From all genes tested, the rs678397 SNP of ACT3N (P = 0.003) and the rs1051771 SNP of TSC2 (P = 0.03) were significantly associated with EARR. No association could be established between other polymorphisms and EARR. In addition, patients with Class III malocclusion and extended treatment times were at increased risk of developing EARR. CONCLUSIONS: Our results support the concept of gene polymorphisms as risk factors in EARR. In particular, a significant association was found between ACT3N and TSC2 and EARR. Clinically, predisposing risk factors for EARR should be assessed for each patient.

Family-based GWAS for dental class I malocclusion and clefts.

BACKGROUND: Individuals born with cleft lip and/or palate who receive corrective surgery regularly have abnormal growth in the midface region such that they exhibit premaxillary hypoplasia. However, there are also genetic contributions to craniofacial morphology in the midface region, so although these individuals appear to have Class III skeletal discrepancy, their molar relationship may be Class I. Past genome-wide association studies (GWASs) on skeletal Class II and III malocclusion suggested that multiple genetic markers contribute to these phenotypes via a multifactorial inheritance model, but research has yet to examine the genetic markers associated with dental Class I malocclusion. Thus, our goal was to conduct a family based GWAS to identify genes across the genome that are associated with Class I malocclusion, as defined by molar relations, in humans with and without clefts. METHODS: Our cohort consisted of 739 individuals from 47 Filipino families originally recruited in 2006 to investigate the genetic basis of orofacial clefts. All individuals supplied blood samples for DNA extraction and genotyping, and a 5,766 single nucleotide polymorphism (SNP) custom panel was used for the analyses. We performed a transmission disequilibrium test for participants with and without clefts to identify genetic contributors potentially involved with Class I malocclusion. RESULTS: In the total cohort, 13 SNPs had associations that reached the genomic control threshold (p < 0.005), while five SNPs were associated with Class I in the cohort of participants without clefts, including four associations that were identified in the total cohort. The associations for the SNPs ABCA4 rs952499, SOX1-OT rs726455, and RORA rs877228 are of particular interest, as past research found associations between these genes and various craniofacial phenotypes, including cleft lip and/or palate. CONCLUSIONS: These findings support the multifactorial inheritance model for dental Class I malocclusion and suggest a common genetic basis for different aspects of craniofacial development.

Genetic and environmental contributions for the relationship between tooth loss and oral potentially malignant disorders and oral squamous cell carcinoma.

BACKGROUND: To investigate the association between tooth loss and oral potentially malignant disorders and oral squamous cell carcinoma, focusing on epidemiological factors and genetic variants. METHODS: Case-control study, including histologically confirmed oral potentially malignant disorders and oral squamous cell carcinoma cases and healthy controls. Unadjusted and adjusted odds ratios for this association were calculated. Single-nucleotides polymorphisms were tested for individuals with and without missing teeth. RESULTS: Case individuals were more edentulous while controls had fewer missing teeth (p = 0.006). There was an increased risk for the outcomes associated with edentulism (OR = 6.95, p = 0.000), even after adjustments for educational level (OR = 4.7, p = 0.034) and smoking habits (OR = 5.01, p = 0.022). Among individuals with tooth loss, rs1533767 (WNT11), rs3923087, and rs11867417 (AXIN2) were associated with the outcomes (OR = 1.67, p = 0.03, OR = 0.53, p = 0.05, and OR = 0.42, p = 0.00, respectively). CONCLUSIONS: Tooth loss could increase the risk for oral potentially malignant disorders and oral squamous cell carcinoma.

The salivary microbiota of patients with acute lower respiratory tract infection-A multicenter cohort study.

The human microbiome contributes to health and disease, but the oral microbiota is understudied relative to the gut microbiota. The salivary microbiota is easily accessible, underexplored, and may provide insight into response to infections. We sought to determine the composition, association with clinical features, and heterogeneity of the salivary microbiota in patients with acute lower respiratory tract infection (LRTI). We conducted a multicenter prospective cohort study of 147 adults with acute LRTI presenting to the emergency department of seven hospitals in three states (Pennsylvania, Michigan, and Ohio) between May 2017 and November 2018. Salivary samples were collected in the emergency department, at days 2-5 if hospitalized, and at day 30, as well as fecal samples if patients were willing. We compared salivary microbiota profiles from patients to those of healthy adult volunteers by sequencing and analyzing bacterial 16-rRNA. Compared to healthy volunteers, the salivary microbiota of patients with LRTI was highly distinct and strongly enriched with intestinal anaerobes such as Bacteroidaceae, Ruminococcaceae, and Lachnospiraceae (e.g., mean 10% relative abundance of Bacteroides vs < 1% in healthy volunteers). Within the LRTI population, COPD exacerbation was associated with altered salivary microbiota composition compared to other LRTI conditions. The largest determinant of microbiota variation within the LRTI population was geography (city in which the hospital was located).

Orthodontics and Genetics

Abstract Introduction: Genetics has been suggested as an explanation for the etiology of malocclusions, although some questions, due to the perception that genetic inheritance is tied to a monogenic or Mendelian form of inheritance. Objective: This paper describes the inheritance of malocclusions, highlighting the areas of knowledge where research has explored mechanisms that explain deviations in patterns of craniofacial growth. Conclusion: Malocclusions have a complex or multifactorial pattern of inheritance, where more than one gene is involved in the development of the phenotype. There is also the possibility that the environment influences malocclusions.

Resumo Introdução: a genética tem sido proposta como uma explicação para a ocorrência das más oclusões, mas isso é questionável, pois a percepção do significado de herança genética está vinculada à herança mendeliana ou monogênica. Objetivo: o presente artigo visa discorrer sobre a herança das más oclusões e ressaltar as áreas do conhecimento nas quais a pesquisa tem explorado mecanismos que explicam a ocorrência de desvios do padrão de crescimento facial. Conclusão: as más oclusões têm um padrão de herança complexo ou multifatorial, no qual mais de um gene está envolvido no desenvolvimento do fenótipo. Isso quer dizer que existe, também, uma potencial influência do ambiente nas más oclusões.

Myosin 1H and the soft tissue profile of african american females with mandibular prognathism

Introduction: The aim of this study was to explore the influence of Myosin 1H on the soft tissue profile of African American females. Methods: Fourteen African American females from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository with the ancestral genotype GG, marker rs10850110, locus 12q24.11 were analyzed. For this investigation, measurements were taken of the eleven items that comprise the Holdaway soft tissue analysis. Profile differences between ethnicity and corresponding normative values were explored by independent-sample t tests for all facial profile measurements. Student's t test for independent means was used to determine differences with accepted norms. Significance was set a p<0.05. Results: There were significant differences between four of the eleven Holdaway values and the reported values for African Americans. The mean convexity value of the African American female group was 1.0 mm less the normative value of 5.7 mm (p>0.000). In contrast, the H angle of the African American females was larger than the normative value. Conclusions: Our study confirms previous research that Myosin 1H contributes to mandibular prognathism. It agrees with the idea that Myosin 1H is less influential in the maxillary soft tissue complex. Understanding the genetic influence of soft tissue growth would allow improved therapies and prevention approaches.

Introduçâo: O objetivo desse estudo foi determinar a influência da miosina 1H nos tecidos moles de mulheres americanas negras. Métodos: Foram estudadas quatorze mulheres americanas negras participantes do projeto Dental Registry and DNA Repository da Faculdade de Odontologia da Universidade de Pittsburgh com o genótipo comum GG do marcador rs10850110, localizado no lócus 12q24.11. Medidas de onze parâmetros que compõem a análise de tecidos moles de Holdaway foram utilizadas. Diferenças entre etnicidade e medidas normais correspondentes, foram exploradas através do teste t de Student de amostras independentes para todas as medidas faciais. O teste t de Student para médias independentes foi usado para determinar diferenças em comparação à medidas normais. A significância foi estabelecida em p<0,05. Resultados: Houve uma diferença estatisticamente significante entre quatro das onze medidas de Holdaway. A convexidade média da mulher americana negra foi de 1,0 mm a menos que o valor normal de 5.7 mm (p>0.000). Em contraste, o ângulo H das mulheres americanas negras foi maior que o valor normal. Conclusões: O nosso estudo confirma resultados anteriores que a miosina 1H contribui para o prognatismo mandibular. Nossos resultados concordam com a ideia de que a miosina 1H tem menor influência nos tecidos moles da maxila. Entender a influência genética no crescimento dos tecidos moles irá possivelmente permitir melhorar as abordagens de tratamento e prevenção atuais.

Kidney disease, increased body mass indexes, and anterior teeth treatment needs

Objective: The purpose of this study was to test the hypothesis that individuals with kidney disease will have more dental issues affecting their anterior teeth. This effect on oral health would be independent from the effects of their higher frequency of obesity. Methods : Using the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository project, anterior teeth treatment history was evaluated for patients with kidney disease. Four thousand nine hundred and eighty-three individuals were evaluated. Individuals with kidney disease were compared to individuals who did not present the condition. Results : One hundred and three individuals reported kidney disease and 1,424 had history of treatment of anterior teeth. Individuals with kidney disease had significant more anterior teeth treatments (p=0.001). Individuals who reported kidney disease also had a higher frequency of overweight individuals, but anterior teeth restoration needs were higher in all individuals with kidney disease, independent of their body mass index. Conclusion : Chronic kidney disease increases treatment needs of anterior teeth and potentially leads to worse oral health outcomes and warrants changes in protocols for treatment of individuals with chronic kidney disease.

Objetivo: O objetivo dessa série de avaliações foi testar a hipótese de que pessoas com doença renal têm mais necessidades de tratamento dos dentes anteriores. Esse efeito seria independente do risco aumentado de ser obeso. Métodos : Através do projeto da Faculdade de Odontologia da Universidade de Pittsburgh entitulado Dental Registry and DNA Repository , foi avaliada a história de tratamento em dentes anteriores em pacientes com doença renal. Quatro mil novecentos e oitenta e três indivíduos foram estudados. Resultados : Cento e três indivíduos reportaram ter doença renal e 1.424 pessoas tinham história de tratamento em dentes anteriores. Indivíduos com doença renal tiveram mais tratamento em dentes anteriores (p=0.001). Pessoas que reportaram doença renal também tiveram uma maior freqüência de obesidade, todavia necessidade de tratamento em dentes anteriores foi maior em indivíduos com doença renal, independente do índice de massa corporal. Conclusão : Doença renal crônica aumenta a necessidade de tratamrnto dos dentes anteriores, o que aumenta a chance de perda dentária e sugere que um protocol diferente para tartar pessoas com doença renal crônica seja uma medida justificada.

Assessing the association between hypoxia during craniofacial development and oral clefts

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.

Edad materna y defectos del tubo neural: evidencia para un efecto mayor en espina bífida que anencefalia / Influence of maternal age on the risk for neural tube defects, a meta analysis

Background: Recent evidence from birth order data suggest that maternal factors can differently influence anencephaly and spina bifida. Aim: To study the influence of maternal age on the risk for neural tube defects. Material and methods: A meta-analysis of published data on neural tube defects (NTDs) was carried out to determine whether there is an increased risk to have a child with NTDs for younger and older mothers and if this risk differs depending on the type of NTD. All data available with information regarding the frequency of live births and NTDs cases by maternal age (five- or ten-year intervals) were included in the analysis. Effect sizes calculations were performed. Results: The analysis supports the hypothesis that there is an increased risk of having an offspring with NTDs for mothers 40 years of age or older. However, this effect is stronger for spina bifida than for anencephaly. There is also evidence that mothers 19 years old or younger have a higher risk for having a child with spina bifida. Conclusions: Maternal age influences the risk of having an offspring with neural tube defects.

Análisis mutacional del gen Homeobox de segmento muscular 1 (MSX1) en chilenos con fisuras orales / Mutational analysis of the muscle segment homeobox gene 1 (MSX1) in Chilean patients with cleft lip/palate

Background: Mutations of the MSX1 gene may contribute to nonsyndromic forms of cleft lip and/or cleft palate. Aim: To search for mutations of MSX1 coding regions, including one highly conserved non-coding region in the single intron, among Chilean patients with cleft lip/palate. Patients and Methods: We studied 45 patients with cleft lip/palate and their parents. Oral mucosa samples were obtained with a swab. DNA was extracted and amplified by PCR. Results: Two missense mutations (G16D and G34A) were identified in this study that may be useful for future admixture studies. The G16D mutation appears to disrupt a possible splicing site and may contribute to clefting in this population. Conclusions: Rare MSX1 mutations are found in some cases of cleft lip and/or cleft palate but others remain to be found most likely in other regulatory regions of the gene.