RESUMO
Aim: To assess the association between PEMT variants and nonsyndromic cleft lip with or without cleft palate in Chile and the effects of these variants on global DNA methylation. Subjects & methods: The authors obtained genotypes for nine variants from 247 cases and 453 controls for genotype-phenotype associations. The effect of significant polymorphisms on global DNA methylation (percentage of long interspersed element-1 methylation) was evaluated in a subsample of 95 controls. Results: After multiple comparison corrections, variants rs7649 and rs4646409 were associated with nonsyndromic cleft lip with or without cleft palate. Carriers of risk alleles presented lower DNA methylation levels than noncarriers. Conclusion: According to functional analysis for risk variants from previous reports, the authors infer that a decrease of methyl group availability is occurring in affected subjects.
This study evaluated if variants in the gene named PEMT confers an increased risk for nonsyndromic cleft lip with or without cleft palate in Chile and its possible effects on methylation of DNA, a variable linked to gene expression modulation. The study found that the variants recognized as rs7649 and rs4646409 increase the risk of nonsyndromic cleft lip with or without cleft palate in the Chilean population and decrease DNA methylation. The authors conclude that this gene may be involved in this birth defect. New studies are needed to confirm the relation between this condition and DNA methylation mediated by these genetic variants.
Assuntos
Fenda Labial , Fissura Palatina , Chile , Fenda Labial/genética , Fissura Palatina/genética , Genótipo , Humanos , Fosfatidiletanolamina N-Metiltransferase/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
The aims of this study were to assess the association between polymorphisms within genes involved in vitamin B12 transport and nonsyndromic cleft lip with or without cleft palate (NSCL/P) and global DNA methylation in Chile. From 247 cases and 453 controls, we obtained variant genotypes for CBLIF, CUBN, AMN, ABCC1, CD320, and TCN2 from a single nucleotide polymorphisms array. Global DNA methylation in 95 controls was obtained through LINE-1 methylation. After multiple comparison corrections, only rs780807 in CUBN remains associated with NSCL/P at dominant model (OR 0.564, p-value = 0.0006, q-value = 0.0450). Carriers of protective allele showed lower levels of DNA methylation than non-carriers (p = 0.0259). Further studies are necessary in order to explain relations with the phenotype and DNA methylation due to the absence of functional evidence for rs780807 in CUBN.
Assuntos
Fenda Labial , Fissura Palatina , Estudos de Casos e Controles , Chile , Fenda Labial/genética , Fissura Palatina/genética , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único , Vitamina B 12RESUMO
The aim of this study was to evaluate, in a case-control design, the association between maternal genotypes for variants in 23 genes involved in folate/one-carbon metabolism and nonsyndromic cleft lip with or without cleft palate (NSCL/P) in a Chilean population. After applying several filters to an Illumina array, we extracted 175 single nucleotide polymorphisms (SNPs) from 150 mothers of NSCL/P cases and 150 control women. Association was evaluated using computed odds ratio (OR) with a 95% confidence interval (95% CI) in additive, recessive, and dominant models. After multiple comparison correction, only SNP rs4451422 (A>C), located 237 bp downstream of the gene encoding the human folylpolyglutamate synthetase (FPGS), maintained a significant association with NSCL/P in the offspring (OR 3.03; 95% CI 1.69-5.26). The variant rs4451422 is associated with a decrease in FPGS expression according to database annotation. Our results lead to a new hypothesis that a lower activity of FPGS enzyme reduces intracellular folate levels and increases the risk of an offspring having NSCL/P.
Assuntos
Fenda Labial , Fissura Palatina , Carbono , Chile , Fenda Labial/genética , Fissura Palatina/genética , Ácido Fólico , Genótipo , HumanosRESUMO
BACKGROUND: The S-adenosyl-methionine (SAM) availability is crucial for DNA methylation, an epigenetic mechanism involved in nonsyndromic cleft lip with or without cleft palate (NSCL/P) expression. The aim of this study was to assess the association between single-nucleotide polymorphisms (SNPs) of genes involved in SAM synthesis and NSCL/P in a Chilean population. METHODS: In 234 cases and 309 controls, 18 SNPs in AHCY, MTR, MTRR, and MAT2A were genotyped, and the association between them and the phenotype was evaluated based on additive (allele), dominant, recessive and haplotype models, by odds ratio (OR) computing. RESULTS: Three deep intronic SNPs of MTR showed a protective effect on NSCL/P expression: rs10925239 (OR 0.68; p = 0.0032; q = 0.0192), rs10925254 (OR 0.66; p = 0.0018; q = 0.0162), and rs3768142 (OR 0.66; p = 0.0015; q = 0.0162). Annotations in expression database demonstrate that the protective allele of the three SNPs is associated with a reduction of MTR expression summed to the prediction by bioinformatic tools of its potentiality to modify splicing sites. CONCLUSIONS: The protective effect against NSCL/P of these intronic MTR SNPs seems to be related to a decrease in MTR enzyme expression, modulating the SAM availability for proper substrate methylation. However, functional analyses are necessary to confirm our findings. IMPACT: SAM synthesis pathway genetic variants are factors associated to NSCL/P. This article adds new evidence for folate related genes in NSCL/P in Chile. Its impact is to contribute with potential new markers for genetic counseling.
Assuntos
5-Metiltetra-Hidrofolato-Homocisteína S-Metiltransferase/genética , Adenosil-Homocisteinase/genética , Fenda Labial/genética , Fissura Palatina/genética , Ferredoxina-NADP Redutase/genética , Metionina Adenosiltransferase/genética , Polimorfismo de Nucleotídeo Único , S-Adenosilmetionina/metabolismo , Alelos , Chile/epidemiologia , Fenda Labial/fisiopatologia , Fissura Palatina/fisiopatologia , Feminino , Frequência do Gene , Genes Dominantes , Genes Recessivos , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Metionina/genética , Razão de ChancesRESUMO
Aim: To evaluate the risk of nonsyndromic orofacial clefts (NSOFCs) associated with LINE-1 methylation, as a marker of global DNA methylation, and the effect of MTHFR functional variants on this variable. Patients & methods: LINE-1 methylation was evaluated by bisulfite modification coupled to DNA pyrosequencing in 95 NSOFC cases and 95 controls. In these subjects, MTHFR genotypes for variants c.C677T (rs1801133) and c.A1298C (rs1801131) were obtained. Results: Middle levels (second tertile) of LINE-1 methylation increase the risk of NSOFCs. In addition, LINE-1 methylation depends on c.A1298C genotypes in controls but not in cases. Conclusion: A nonlinear association between global DNA methylation and NSOFCs was detected in this Chilean population, which appears to be influenced by MTHFR functional variants.
Assuntos
Encéfalo/anormalidades , Fenda Labial/genética , Fissura Palatina/genética , Metilação de DNA , Elementos Nucleotídeos Longos e Dispersos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , Chile , Humanos , Lactente , Recém-Nascido , Polimorfismo de Nucleotídeo ÚnicoRESUMO
OBJECTIVE: To assess the association between polymorphic variants from SHMT1 and MTHFS genes, involved in the cytoplasmic futile folate cycle, and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in the Chilean population. SUBJECTS AND METHODS: In a sample of 139 Chilean NSCL/P cases and 278 controls, we obtained the genotypes for nine variants of SHMT1 and MTHFS and the association between them and the phenotype was evaluated using odds ratios (OR) in additive (allele), dominant, and recessive models. RESULTS: After correction for multiple comparisons, only the variant rs1979277 (G > A; p.Leu474Phe) from SHMT1 showed a significant and protective effect for additive (OR 0.60; 95% CI 0.42-0.86; p = .0054, q = 0.0488) and dominant models (OR 0.48; 95% CI 0.29-0.75; p = .0009; q = 0.0081). Our bioinformatic prediction plus functional evidence from previous reports demonstrate that the A allele for this missense variant decreases the enzymatic activity. CONCLUSIONS: Owing to the rs1979277 A allele, which reduces the cytoplasmic SHMT activity and has a higher frequency in controls than in NSCL/P cases, we hypothesized that a low enzyme activity may increase the cytoplasmic concentration of folates and, therefore, explain the protective role against OFCs.
Assuntos
Fenda Labial/genética , Fissura Palatina/genética , Glicina Hidroximetiltransferase/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Chile , Feminino , Genótipo , Humanos , MasculinoRESUMO
El Ligamento Discomaleolar es una estructura que no se describe en los textos clásicos de anatomía a pesar de ser descrito por primera vez por Rees, Pinto y luego por diversos autores como una estructura ligamentosa de tejido fibroelástico que conecta el cuello y el proceso anterior del martillo a través de la fisura petrotimpánica hasta la parte medioposterosuperior de la cápsula de la articulación temporomandibular (ATM), el disco articular y el ligamento esfenomandibular. Diversos estudios han reportado las implicaciones clínicas del ligamento discomaleolar y la relación entre los trastornos temporomandibulares con los síntomas asociados al oído medio. El objetivo de este estudio fue realizar una revisión sobre estudios que describen el ligamento discomaleolar y determinar si se considera una estructura independiente anatómica y funcionalmente y su relación con el oído medio. Se realizó una búsqueda de literatura científica identificó artículos donde se identifican las estructuras anatómicas asociadas a la articulación témporomandibular y el oído medio, fueron seleccionados 24 artículos según los criterios de selección. Los resultados obtenidos en los estudios seleccionados en esta revisión sugieren la existencia de una lámina o fascículo fibroso que conecta el disco de la ATM con el maléolo del oído medio, lo que validaría la presencia y relación entre el ligamento discomaleolar y los trastornos del oído medio.
The Discomaleolar Ligament is a structure that is not described in the classic texts of anatomy despite being described for the first time by Rees, Pinto and later by various authors as a ligamentous structure of fibroelastic tissue that connects the neck and the anterior process of the malleus through the petrotympanic cleft to the mid-superior part of the capsule of the temporomandibular joint (TMJ), the articular disc and the sphenomandibular ligament. Several studies have reported the clinical implications of the discomaleolar ligament and the relationship between temporomandibular disorders and symptoms associated with the middle ear. The aim of this study was to conduct a review of studies that describe the discomaleolar ligament and determine if an anatomically and functionally independent structure and its relation to the middle ear is considered. A search was performed of scientific literature identified articles where the anatomical structures associated with the temporomandibular joint and the middle ear were identified, 24 articles were selected according to the selection criteria. The results obtained in the studies selected in this review suggest the existence of a lamina or fibrous fascicle that connects the TMJ disc with the malleolus of the middle ear, which would validate the presence and relationship between the discomaleolar ligament and middle ear disorders.
Assuntos
Humanos , Articulação Temporomandibular/anatomia & histologia , Ligamentos Articulares/anatomia & histologia , Martelo/anatomia & histologiaRESUMO
SUMMARY: The temporomandibular joint (TMJ) is composed of bony structures, cartilage, capsule, articular disc, synovial membrane and ligaments. Some authors consider the "Tanaka ligament" described in the 1980s by Terry Tanaka as an intra-capsular ligament of the TMJ that unites medially the articular disc and mandibular fossa. The aim of the present study was to analyze the use of the term "Tanaka ligament" in the literature evaluating the scientific support of its existence. A literature review was carried out under the terms "Tanaka Ligament [AND] TMJ" and "Ligamento Tanaka [AND] ATM" (Spanish and Portuguese) in the search engines: MEDLINEPubmed, Science Direct, Google Scholar, LILACS-Bireme and SciELO. Scientific articles and theses were considered in English, Spanish and Portuguese. A total of 1,355 studies were found, summing up the results of all the search engines, of which 8 studies (5 articles and 3 theses) were selected after applying inclusion and exclusion criteria, selection by title, abstract and content. Most of these studies were discarded because they had contents related to the TMJ and/or ligaments wherein an author used the surname "Tanaka", that were not related to the Tanaka ligament. Among the 8 selected studies, 6 of them cite text books, 1 cites a video published by Terry Tanaka and 1 cites a thesis. Most of these textbooks cited also refer to videos by Terry Tanaka and his books. Moreover, most of the anatomical literature does not consider this ligament as an individualized structure. Although there are descriptions of Tanaka's ligament in textbooks, the scientific support of its existence is based only on videos and texts by Terry Tanaka. The dissemination of knowledge associated with this ligament must be cautious, as there is a need for further morphological and functional studies to confirm its existence.
RESUMEN: La articulación temporomandibular (TMJ) se compone de estructuras óseas, cartílago, cápsula, disco articular, membrana sinovial y ligamentos. Algunos autores consideran el "ligamento de Tanaka" descrito en los años 80 por Terry Tanaka como un ligamento intra-capsular de la ATM que une medialmente el disco articular y la fosa mandibular. El objetivo del presente estudio fue analizar el uso del término "ligamento de Tanaka" en la literatura evaluando el soporte científico de su existencia. Se realizó una revisión de la literatura bajo los términos "Tanaka Ligament [AND] TMJ" y "Ligamento Tanaka [AND] ATM" (Español y Portugués) en los buscadores: MEDLINE-Pubmed, Science Direct, Google Académico, LILACS-Bireme y SciELO. Se consideraron artículos científicos y tesis en inglés, español y portugués. Se obtuvieron un total de 1.355 estudios, sumando los resultados de todos los motores de búsqueda, de los cuales se seleccionaron 8 estudios (5 artículos y 3 tesis) después de aplicar los criterios de inclusión y exclusión y la selección por título, resumen y contenido. La mayoría de estos estudios fueron descartados porque tenían contenidos relacionados con la ATM y/o ligamentos cuyo autor tenía el apellido "Tanaka", que no estaba relacionado con el ligamento de Tanaka. Entre los 8 estudios seleccionados, 6 de ellos citan libros de texto, uno cita un video publicado por Terry Tanaka y otro cita una tesis. La mayoría de estos libros citados también se refieren a los videos de Terry Tanaka y sus libros. Además, la mayor parte de la literatura anatómica no considera este ligamento como una estructura individualizada. Aunque hay descripciones del ligamento de Tanaka en los libros de texto, el apoyo científico de su existencia se basa sólo en videos y textos de Terry Tanaka. La difusión del conocimiento asociado a este ligamento debe ser cautelosa, revelando la necesidad de más estudios morfológicos y funcionales para confirmar su existencia.
Assuntos
Humanos , Ligamentos/anatomia & histologia , Articulação Temporomandibular/anatomia & histologiaRESUMO
The aim of this study was to analyze the influence of three different transmucosal heights of the abutments in single and multiple implant-supported prostheses through the finite element method. External hexagon implants, MicroUnit, and EsthetiCone abutments were scanned and placed in an edentulous maxillary model obtained from a tomography database. The simulations were divided into two groups: (1) one implant with 3.75 × 10 mm placed in the upper central incisor, simulating a single implant-supported fixed prosthesis with an EsthetiCone abutment; and (2) two implants with 3.75 × 10 mm placed in the upper lateral incisors with MicroUnit abutments, simulating a multiple implant-supported prosthesis. Subsequently, each group was subdivided into three models according to the transmucosal height (1, 2, and 3 mm). A static oblique load at an angle of 45 degrees to the long axis of the implant in palatal-buccal direction of 150 and 75 N was applied for multiple and single implant-supported prosthesis, respectively. The implants and abutments were assessed according to the equivalent Von Mises stress analyses while the bone and ceramics were analyzed through maximum and minimum principal stresses. The total deformation values increased in all models, while the transmucosal height was augmented. The transmucosal height of the abutments influences the stress values at the bone, ceramics, implants, and abutments of both the single and multiple implant-supported prostheses, with the transmucosal height of 1 mm showing the lowest stress values.
Assuntos
Dente Suporte , Planejamento de Prótese Dentária , Prótese Dentária Fixada por Implante , Análise de Elementos Finitos , Imageamento Tridimensional , Dinâmica não Linear , Simulação por Computador , Análise do Estresse Dentário , Humanos , Modelos Teóricos , Estresse MecânicoRESUMO
We present the case of a 13-year-old patient with bilateral transmigration of mandibular canine associated with multiple composite odontoma. Impacted canines are very uncommon, with a 0.1 % to 3.6 % prevalence of appearance. The presence in the mandible is less frequent. The odontoma development is often associated with the impacted canines. The etiology is unknown but is associated with traumatic, infectious, hereditary or genetic factors. This pathology is asymptomatic and associated with eruption disorders in temporal and permanent dentition.
Presentamos el caso de un paciente de 13 años de edad con trasmigración bilateral de canino mandibular asociado a múltiples odontomas compuestos. Los caninos impactados son muy poco frecuentes, con una prevalencia de aparición de 0,1 % a 3,6 %. La presencia en la mandíbula es menos frecuente. El desarrollo de odontomas se asocia a menudo con los caninos impactados. La etiología es desconocida pero está asociada con factores traumáticos, infecciosos, hereditarios o genéticos. Esta patología es asintomática y está asociada a trastornos de erupción en dentición temporal y permanente.