RESUMEN
Dental caries remains the most common chronic childhood disease. Despite strong evidence of genetic components, there have been few studies of candidate genes and caries. In this analysis we tried to assess genetic and environmental factors contributing to childhood caries in the Iowa Fluoride Study. Environmental factors (age, sex, race, tooth-brushing frequencies and water fluoride level) and three dental caries scores (d(2)fs-total, d(2)fs-pit/fissure, and d(2)fs-smooth surface) were assessed in 575 unrelated children (mean age 5.2 years). Regression analyses were applied to assess environmental correlates. The Family-Based Association Test was used to test genetic associations for 23 single nucleotide polymorphism (SNP) markers in 7 caries candidate genes on 333 Caucasian parent-child trios. We evaluated the associations between caries status and the level of both single and multiple SNPs (haplotype) respectively. Permutation procedure was performed for correction of inflated type I errors due to multiple testing. Age, tooth-brushing frequency and water fluoride level were significantly correlated to at least one carious score. Caries on pit and fissure surfaces was substantially higher than on smooth surfaces (61 vs. 39%). SNPs in three genes (DSPP, KLK4 and AQP5) showed consistent associations with protection against caries. Of note, KLK4 and AQP5 were also highlighted by subsequent haplotype analysis. Our results support the concept that genes can modify the susceptibility of caries in children. Replication analysis in independent cohorts is highly needed in order to verify the validity of our findings.
Asunto(s)
Acuaporina 5/genética , Susceptibilidad a Caries Dentarias/genética , Caries Dental/genética , Proteínas de la Matriz Extracelular/genética , Calicreínas/genética , Fosfoproteínas/genética , Sialoglicoproteínas/genética , Diente Primario/patología , Factores de Edad , Niño , Preescolar , Índice CPO , Caries Dental/etiología , Etnicidad , Femenino , Fluoruros/análisis , Interacción Gen-Ambiente , Estudios de Asociación Genética , Humanos , Iowa , Masculino , Polimorfismo de Nucleótido Simple , Análisis de Regresión , Factores Sexuales , Encuestas y Cuestionarios , Cepillado Dental/estadística & datos numéricos , Abastecimiento de AguaRESUMEN
MSX1 has been considered a strong candidate for orofacial clefting, based on mouse expression studies and knockout models, as well as association and linkage studies in humans. MSX1 mutations are also causal for hereditary tooth agenesis. We tested the hypothesis that individuals with orofacial clefting with or without tooth agenesis have MSX1 coding mutations by screening 33 individuals with cleft lip with or without cleft palate (CL/P) and 19 individuals with both orofacial clefting and tooth agenesis. Although no MSX1 coding mutations were identified, the known 101C > G variant occurred more often in subjects with both CL/P and tooth agenesis (p = 0.0008), while the *6C-T variant was found more often in CL/P subjects (p = 0.001). Coding mutations in MSX1 are not the cause of orofacial clefting with or without tooth agenesis in this study population. However, the significant association of MSX1 with both phenotypes implies that MSX1 regulatory elements may be mutated.
Asunto(s)
Anodoncia/genética , Labio Leporino/genética , Fisura del Paladar/genética , Factor de Transcripción MSX1/genética , Adolescente , Estudios de Casos y Controles , Niño , Codón/genética , Citosina , Femenino , Ligamiento Genético/genética , Guanina , Humanos , Masculino , Mutación/genética , Sistemas de Lectura Abierta/genética , Fenotipo , Elementos Reguladores de la Transcripción/genética , Análisis de Secuencia de ADN , TiminaRESUMEN
MSX1 has a critical role in craniofacial development, as indicated by expression assays and transgenic mouse phenotypes. Previously, MSX1 mutations have been identified in three families with autosomal-dominant tooth agenesis. To test the hypothesis that MSX1 mutations are a common cause of congenital tooth agenesis, we screened 92 affected individuals, representing 82 nuclear families, for mutations, using single-strand conformation analysis. A Met61Lys substitution was found in two siblings from a large family with autosomal-dominant tooth agenesis. Complete concordance of the mutation with tooth agenesis was observed in the extended family. The siblings have a pattern of severe tooth agenesis similar that in to previous reports, suggesting that mutations in MSX1 are responsible for a specific pattern of inherited tooth agenesis. Supporting this theory, no mutations were found in more common cases of incisor or premolar agenesis, indicating that these have a different etiology.
Asunto(s)
Anodoncia/genética , Proteínas de Homeodominio/genética , Factores de Transcripción , Adolescente , Adulto , Sustitución de Aminoácidos , Niño , Preescolar , Análisis Mutacional de ADN , Salud de la Familia , Genes Dominantes , Genes Homeobox , Ligamiento Genético , Humanos , Factor de Transcripción MSX1 , Persona de Mediana Edad , Mutación Missense , Odontogénesis/genética , Polimorfismo Conformacional Retorcido-SimpleRESUMEN
The purpose of this retrospective longitudinal study was to compare 7 cephalometric measurements of the cranial base in subjects with Class I and Class II skeletal patterns at ages 1 month, 2 years, and 14 years. A sample of 22 Class I and 21 Class II subjects was selected; the inclusion criteria were overjet, ANB, and Harvold unit difference. Analyses of head circumference, crown-rump length, and weight revealed no significant (P >.15) differences between the Class I and Class II infant subjects at the initial age (1 month). One angular and 6 linear measurements were first compared with a multivariate analysis of variance, which revealed significant effects for age (P <.0001) and the age by skeletal pattern interaction (P =.0266) but not for skeletal pattern (P =.3705). Analyses of variance showed significant (P <.0001) age effects for each of the cephalometric variables but no significant skeletal pattern effects (P >.10). The anterior cranial base measurement of nasion to sphenoethmoidal suture was the only variable found to have a significant age by skeletal pattern interaction (P <.006), which revealed a difference in the timing of its growth spurt that occurred between 1 month and 2 years in the Class I subjects and between 2 years and 14 years in the Class II subjects. There were no significant differences between the skeletal classes at any of the 3 ages evaluated. Conclusions from this study indicate that cranial base growth patterns are similar for Class I and Class II subjects and that the premise of a more obtuse "saddle angle" or cranial base angle in Class II skeletal patterns was not supported.