RESUMEN
This study evaluated associations between craniofacial candidate genes and skeletal variation in patients with malocclusion. Lateral cephalometric radiographs of 269 untreated adults with skeletal classes I, II, and III malocclusion were digitized with 14 landmarks. Two-dimensional coordinates were analyzed using Procrustes fit and principal component (PC) analysis to generate continuous malocclusion phenotypes. Skeletal class classifications (I, II, or III) were used as a categorical phenotype. Individuals were genotyped for 198 single-nucleotide polymorphisms (SNPs) in 71 craniofacial genes and loci. Phenotype-genotype associations were tested via multivariate linear regression for continuous phenotypes and multinomial logistic regression for skeletal malocclusion class. PC analysis resulted in 4 principal components (PCs) explaining 69% of the total skeletal facial variation. PC1 explained 32.7% of the variation and depicted vertical discrepancies ranging from skeletal deep to open bites. PC1 was associated with a SNP near PAX5 (P = 0.01). PC2 explained 21.7% and captured horizontal maxillomandibular discrepancies. PC2 was associated with SNPs upstream of SNAI3 (P = 0.0002) and MYO1H (P = 0.006). PC3 explained 8.2% and captured variation in ramus height, body length, and anterior cranial base orientation. PC3 was associated with TWIST1 (P = 0.000076). Finally, PC4 explained 6.6% and detected variation in condylar inclination as well as symphysis projection. PC4 was associated with PAX7 (P = 0.007). Furthermore, skeletal class II risk increased relative to class I with the minor alleles of SNPs in FGFR2 (odds ratio [OR] = 2.1, P = 0.004) and declined with SNPs in EDN1 (OR = 0.5, P = 0.007). Conversely, skeletal class III risk increased versus class I with SNPs in FGFR2 (OR 2.2, P = 0.005) and COL1A1 (OR = 2.1, P = 0.008) and declined with SNPs in TBX5 (OR = 0.5, P = 0.014). PAX5, SNAI3, MYO1H, TWIST1, and PAX7 are associated with craniofacial skeletal variation among patients with malocclusion, while FGFR2, EDN1, TBX5, and COL1A1 are associated with type of skeletal malocclusion.
Asunto(s)
Estudios de Asociación Genética , Maloclusión de Angle Clase III/genética , Maloclusión Clase II de Angle/genética , Maloclusión Clase I de Angle/genética , Adolescente , Adulto , Anciano , Puntos Anatómicos de Referencia/patología , Cefalometría/métodos , Colágeno Tipo I/genética , Cadena alfa 1 del Colágeno Tipo I , Proteínas de Unión al ADN/genética , Genotipo , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Maloclusión Clase I de Angle/patología , Maloclusión Clase II de Angle/patología , Maloclusión de Angle Clase III/patología , Mandíbula/patología , Persona de Mediana Edad , Miosina Tipo I , Proteínas Nucleares/genética , Mordida Abierta/genética , Sobremordida/genética , Factor de Transcripción PAX5/genética , Factor de Transcripción PAX7/genética , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Factores de Transcripción de la Familia Snail , Proteínas de Dominio T Box/genética , Factores de Transcripción/genética , Proteína 1 Relacionada con Twist/genética , Adulto Joven , Dedos de Zinc/genéticaRESUMEN
INTRODUCTION: α-Actinins are myofibril anchor proteins that influence the contractile properties of skeletal muscles. ACTN2 is expressed in slow type I and fast type II fibers, whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (ie, changing 577RR to 577XX, the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminishes fast contractile ability, enhances endurance performance, and reduces bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in the masseter muscle of orthognathic surgery patients to determine the genotype associations with malocclusion. METHODS: Clinical information, masseter muscle biopsies, and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 single nucleotide polymorphisms, real-time polymerase chain reaction quantitation of muscle gene message, and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. RESULTS: Muscle mRNA expression level was significantly different for ACTN3 single nucleotide polymorphism genotypes (P <0.01). The frequency of ACTN3 genotypes was significantly different for the sagittal and vertical classifications of malocclusion, with the clearest association being elevated 577XX genotype in skeletal Class II malocclusion (P = 0.003). This genotype also resulted in significantly smaller diameters of fast type II fibers in masseter muscles (P = 0.002). CONCLUSION: ACTN3 577XX is overrepresented in subjects with skeletal Class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in subjects with deepbite malocclusion, suggesting that muscle differences contribute to variations in vertical facial dimensions.
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Actinina/genética , Arginina/genética , Maloclusión Clase II de Angle/genética , Sobremordida/genética , Polimorfismo Genético/genética , Biopsia , Codón de Terminación/genética , Citosina , Exones/genética , Femenino , Frecuencia de los Genes/genética , Variación Genética/genética , Genotipo , Humanos , Intrones/genética , Masculino , Músculo Masetero/metabolismo , Músculo Masetero/patología , Fibras Musculares de Contracción Rápida/ultraestructura , Fibras Musculares Esqueléticas/clasificación , Fibras Musculares Esqueléticas/patología , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Saliva/química , Timina , Adulto JovenRESUMEN
INTRODUCTION: Genetic influences on the development of malocclusion include heritable effects on both masticatory muscles and jaw skeletal morphology. Beyond genetic variations, however, the characteristics of muscle and bone are also influenced by epigenetic mechanisms that produce differences in gene expression. We studied 2 enzymes known to change gene expressions through histone modifications, chromatin-modifying histone acetyltransferase KAT6B and deacetylase HDAC4, to determine their associations with musculoskeletal variations in jaw deformation malocclusions. METHODS: Samples of masseter muscle were obtained from subjects undergoing orthognathic surgery from 6 malocclusion classes based on skeletal sagittal and vertical dysplasia. The muscles were characterized for fiber type properties by immunohistochemistry, and their total RNA was isolated for gene expression studies by microarray analysis and quantitative real-time polymerase chain reaction. RESULTS: Gene expressions for fast isoforms of myosins and contractile regulatory proteins and for KAT6B and HDAC4 were severalfold greater in masseter muscles from a patient with a deepbite compared with one with an open bite, and genes related to exercise and activity did not differ substantially. In the total population, expressions of HDAC4 (P = 0.03) and KAT6B (P = 0.004) were significantly greater in subjects with sagittal Class III than in Class II malocclusion, whereas HDAC4 tended to correlate negatively with slow myosin type I and positively with fast myosin gene, especially type IIX. CONCLUSIONS: These data support other published reports of epigenetic regulation in the determination of skeletal muscle fiber phenotypes and bone growth. Further investigations are needed to elucidate how this regulatory model might apply to musculoskeletal development and malocclusion.
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Epigenómica , Histona Acetiltransferasas/genética , Histona Desacetilasas/genética , Músculo Masetero/efectos de los fármacos , Mordida Abierta/genética , Sobremordida/genética , Proteínas Represoras/genética , Femenino , Histona Acetiltransferasas/farmacología , Histona Desacetilasas/farmacología , Humanos , Masculino , Maloclusión Clase II de Angle/genética , Maloclusión de Angle Clase III/genética , Miosinas/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Represoras/farmacología , Adulto JovenRESUMEN
OBJECTIVE: The aim of this study was to report the case of a Japanese subject with ring chromosome 18 syndrome. A cephalometric analysis was performed, and the treatment procedure is described. DESIGN: Lateral and posteroanterior cephalograms were compared with Japanese norms. Dental anomalies were evaluated by a model analysis. The outcome of orthodontic-prosthodontic treatment was evaluated by comparing cephalograms during the course of treatment. RESULTS: The cephalometric analysis showed a reduction in the cranial base length and cranial width, midfacial depth, and height and width. Comparison of lateral cephalograms at age 16 years 6 months and 22 years 4 months showed late growth of the mandible. The model analysis showed that all of the teeth, except for the mandibular canine, were small. CONCLUSIONS: Characteristic craniofacial and dental anomalies were clarified. Successful oral rehabilitation was achieved by combined orthodontic-prosthodontic treatment.