RESUMEN
AIM: Evidence suggests caries experience is higher in children with asthma. This study compared caries experience in asthmatic and non-asthmatic children and defined whether variation in the distribution of caries experience differed between the two groups and was dependent on the presence of genetic variation in enamel formation genes. METHODS: Children with asthma were recruited at the Istanbul University, Faculty of Medicine, Department of Paediatrics, Division of Paediatric Allergy and Pulmonary Diseases, and non-affected children were recruited at the Istanbul University, Faculty of Dentistry, Department of Paedodontics. Cases (N = 100) were defined as children between the ages of 6 and 12 years with asthma and controls (N = 100) as children without asthma. Cases and controls were matched by sex and age. All study subjects received a complete dental exam, provided demographic and other caries and asthma risk factors data, and a saliva sample for DNA extraction. Caries experience was defined based on DMFT/dmft and DMFS/dmfs scores. Genotypes of 11 SNPs were selected in intronic regions of enamel development genes. PCR with TaqMan chemistry was used for genotyping all selected markers. Association between caries experience (caries-free versus caries affected) depending on asthma status and SNPs was tested with PLINK by logistic regression, adjusting by risk, and other preventive measures. p values below 0.0045 (0.05/11) were considered statistically significant. RESULTS: Logistic regression analysis showed an association between AMBN rs4694075 and caries experience (p = 2.525e-007). CONCLUSIONS: This study provides, for the first time, evidence that ameloblastin is associated with caries in asthmatic children.
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Asma/complicaciones , Índice CPO , Proteínas del Esmalte Dental/genética , Variación Genética/genética , Amelogénesis/genética , Amelogenina/genética , Estudios de Casos y Controles , Niño , Caries Dental/complicaciones , Caries Dental/genética , Índice de Placa Dental , Proteínas de la Matriz Extracelular/genética , Femenino , Genotipo , Humanos , Intrones/genética , Masculino , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple/genética , Factores de Empalme de ARN , Timina , Cepillado DentalRESUMEN
INTRODUCTION: The majority of tooth agenesis cases are mild (hypodontia) and typically not associated with the gene mutations linked to oligodontia. From this, we hypothesise that most cases of tooth agenesis fit a polygenic mode of inheritance, where several genes with small effects cause a variety of varying phenotypes. MATERIALS AND METHODS: In this study, we looked at 18 not typically studied genes in this condition, to ascertain their contribution to hypodontia. Our study subjects consisted of 167 patients with hypodontia and their parents from two cohorts (one from Brazil and one from Turkey). An additional 465 DNA samples (93 cases with hypodontia and 372 controls without family history for tooth agenesis or oral clefts) from Brazil were also available for this study. Ninety-three single nucleotide polymorphisms that maximally represent the linkage disequilibrium structure of the genes for the 18 genes were selected and genotyped using Taqman chemistry. Chi square was used to test if genotype distributions were in Hardy-Weinberg equilibrium, and 24 markers that were in Hardy-Weinberg equilibrium and had allele frequencies higher than 5 % in a panel of 50 CEPH samples were further tested. Association between hypodontia and genetic variants was tested with the transmission disequilibrium test within the programme Family-Based Association Test (FBAT) and by using Chi square and Fisher's exact tests. Alpha at a level of 0.05 was used to report results. RESULTS: Results suggest possible associations between several genes and hypodontia in the three populations. In the Turkish cohort (n = 51 parent-affected child trios) the most significant results were as follows: FGF3 rs1893047, p = 0.08; GLI3 rs929387, p = 0.03; GLI3 haplotype rs929387-rs846266, p = 0.002; and PAX9 rs2073242, p = 0.03. In the Brazilian cohort (n = 116 parent-affected child trios), the results were as follows: DLX1 rs788173, p = 0.07; FGF3 rs12574452, p = 0.03; GLI2 rs1992901, p = 0.03; and PITX2 rs2595110, p = 0.01. The second Brazilian cohort also suggested that FGF3 (rs12574452, p = 0.01) is associated with hypodontia and added EDAR (rs17269487, p = 0.04), LHX6 (rs989798, p = 0.02), and MSX1 (rs12532, p = 0.003). CONCLUSION: Our results suggest that several genes are potentially associated with hypodontia and their individual contributions may be modest. Hence, these cases may not be explained by inactivating mutations such as many oligodontia cases segregating in a Mendelian fashion but rather are influenced by one or more susceptibility alleles in multiple small effect genes.
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Anodoncia , Frecuencia de los Genes , Anodoncia/genética , Estudios de Casos y Controles , Genotipo , Humanos , Fenotipo , Polimorfismo de Nucleótido SimpleRESUMEN
Caries is a multifactorial disease and little is still known about the host genetic factors influencing susceptibility. Our previous genome-wide linkage scan has identified the interval 5q12.1-5q13.3 as linked to low caries susceptibility in Filipino families. Here we fine-mapped this region in order to identify genetic contributors to caries susceptibility. Four hundred and seventy-seven subjects from 72 pedigrees with similar cultural and behavioral habits and limited access to dental care living in the Philippines were studied. DMFT scores and genotype data of 75 single-nucleotide polymorphisms were evaluated in the Filipino families with the Family-Based Association Test. For replication purposes, a total 1,467 independent subjects from five different populations were analyzed in a case-control format. In the Filipino cohort, statistically significant and borderline associations were found between low caries experience and four genes spanning 13 million base pairs (PART1, ZSWIM6, CCNB1, and BTF3). We were able to replicate these results in some of the populations studied. We detected PART1 and BTF3 expression in whole saliva, and the expression of BTF3 was associated with caries experience. Our results suggest BTF3 may have a functional role in protecting against caries.
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Mapeo Cromosómico/métodos , Cromosomas Humanos Par 5/genética , Susceptibilidad a Caries Dentarias/genética , Caries Dental/genética , Estudios de Casos y Controles , Índice CPO , Caries Dental/prevención & control , Humanos , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple , Proteínas y Péptidos Salivales/genética , Factores de Transcripción/genéticaRESUMEN
Individuals with clefts present considerably more dental anomalies than individuals without clefts. We also have shown that these individuals report cancer in their families more often than do unaffected individuals. We investigated how these conditions correlated with genetic variants associated with clefts to ascertain if specific molecular signatures exist that could help identify individuals at risk for having offspring with these defects. We examined 573 individuals, 158 with clefts, 254 unaffected family members, and 161 non-related controls. Several clinical features, such as laterality, the presence of dental anomalies, medical history, and pregnancy history, were used to assess each individual's cleft status. Then, we performed molecular studies with genes that have been independently associated with oral clefts. We analyzed two datasets: nuclear families and case-control individuals where the case was the child from the family and controls were unrelated non-clefted individuals. In the family data, we confirmed association between clefts and rs987525 on chromosome 8 (p = 0.007) and found an association with rs987525 and tooth agenesis (p = 0.0003). In the case-control data, clefts, supernumerary teeth and familial cancer history were associated with ABCA4-rs481931 on chromosome 1 (p = 2E-19, 0.0007, 2E-06, respectively), and clefts and microdontia were associated with rs1325474 on chromosome 6 (p = 1E-06, 0.0002, respectively).
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Cromosomas Humanos Par 1/genética , Cromosomas Humanos Par 6/genética , Cromosomas Humanos Par 8/genética , Labio Leporino/genética , Fisura del Paladar/genética , Estudio de Asociación del Genoma Completo , Anomalías Dentarias/genética , Adolescente , Adulto , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Niño , Preescolar , Labio Leporino/etiología , Fisura del Paladar/etiología , Salud de la Familia , Femenino , Marcadores Genéticos , Humanos , Desequilibrio de Ligamiento , Modelos Logísticos , Masculino , Anamnesis , Persona de Mediana Edad , Neoplasias/genética , Polimorfismo de Nucleótido Simple , Embarazo , Efectos Tardíos de la Exposición Prenatal , Factores de Riesgo , Fumar/efectos adversos , Anomalías Dentarias/complicaciones , Adulto JovenRESUMEN
There is evidence for a genetic component in caries susceptibility, and studies in humans have suggested that variation in enamel formation genes and their interaction with Streptococcus mutans levels may contribute to caries. For the present study, we used DNA samples collected from 173 unrelated children from Istanbul: 91 children with 4 or more affected tooth surfaces and 82 caries-free children. Six single-nucleotide polymorphism markers were genotyped in selected candidate genes (ameloblastin, amelogenin, enamelin, tuftelin 1 and tuftelin interacting protein 11) that influence enamel formation. Allele and genotype frequencies were compared between groups with distinct caries experience. Regression analysis was used for the evaluation of individual gene effects, environmental effects and gene-environment interactions. Overrepresentation of the C allele of the amelogenin marker was seen in cases with dmft scores higher than 8 (p = 0.01) when compared to controls. Also, overrepresentation of the T allele of the ameloblastin marker was seen in cases with dmfs scores higher than 10 (p = 0.05) when compared to controls. In addition, the CT genotype of the tuftelin rs3790506 marker was overrepresented in cases with dmft scores higher than 5 (p = 0.05) and dmfs scores higher than 6 (p = 0.05) compared to controls. The best-fitting model showed that dmfs is increased when the following factors are present: (1) females and both the anterior and posterior teeth are affected simultaneously, (2) when the T allele of the tuftelin rs3790506 is involved, and (3) the C allele of the amelogenin rs17878486 is involved. Our study provides support that genes involved in enamel formation modify caries susceptibility in humans.
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Amelogénesis/genética , Índice CPO , Amelogenina/genética , Preescolar , Citosina , Caries Dental/microbiología , Susceptibilidad a Caries Dentarias/genética , Proteínas del Esmalte Dental/genética , Ambiente , Femenino , Frecuencia de los Genes/genética , Marcadores Genéticos/genética , Genotipo , Humanos , Masculino , Proteínas Nucleares , Fenotipo , Polimorfismo de Nucleótido Simple/genética , Factores de Empalme de ARN , Saliva/microbiología , Factores Sexuales , Streptococcus mutans/aislamiento & purificación , Timina , TurquíaRESUMEN
There is evidence for a genetic component in caries susceptibility, but the disease is greatly influenced by environmental factors, which are extremely difficult to control in humans. For the present study, we used DNA samples collected from 110 unrelated, non-cleft individuals older than 12 years of age from Tiquisate, Guatemala: a population with similar cultural, dietary and hygiene habits, similar access to the dentist and fluoride exposure. Forty-four individuals were designated 'very low caries experience' (DMFT < or = 2), and 66 were designated 'higher caries experience' (DMFT > or = 3). Single-nucleotide polymorphism markers were genotyped in selected candidate genes (ameloblastin, amelogenin, enamelin, tuftelin-1, and tuftelin interacting protein 11) that influence enamel formation. Having at least one copy of the rare amelogenin marker allele was associated with increased age-adjusted caries experience. This association was stronger in individuals with higher DMFT (DMFT > or = 20; p = 0.0000001). Our results suggest that variation in amelogenin may contribute to caries susceptibility in the population studied. The approach of comparing individuals with extremely distinct caries experiences could be valuable for decreasing the potential influence of environmental factors on genetic studies of caries.
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Amelogenina/genética , Susceptibilidad a Caries Dentarias/genética , Caries Dental/genética , Adolescente , Adulto , Cromosomas Humanos X , Índice CPO , Femenino , Frecuencia de los Genes , Guatemala , Humanos , Indígenas Centroamericanos/genética , Modelos Lineales , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido SimpleRESUMEN
The relativistic solar particle event of 4 May 1960, resulting in a cosmic ray ground level enhancement, occurred well before modern analysis techniques were available. We have located surviving data from 23 neutron monitors and have used these to estimate the spectrum, mean arrival direction and particle pitch angle distribution as the event progressed. We find that the apparent particle arrival direction was at equatorial latitudes, over northern South America, in contrast to contemporary analyses that proposed it to be over North America. Our modified power law spectra are broadly consistent with earlier results. Data from stations above sea level need to be corrected for altitude using a two-attenuation length technique. The standard method involves comparison of data from two relatively close stations at significantly different altitude. We have shown that this method may be unreliable in cases, such as this, of quite sharp anisotropy.
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Radiación Cósmica , Neutrones , Protones , Monitoreo de Radiación , Actividad Solar , Anisotropía , Planeta Tierra , América del Norte , América del SurRESUMEN
The large-scale structure in the distribution of galaxies is thought to arise from the gravitational instability of small fluctuations in the initial density field of the Universe. A key test of this hypothesis is that forming superclusters of galaxies should generate a systematic infall of other galaxies. This would be evident in the pattern of recessional velocities, causing an anisotropy in the inferred spatial clustering of galaxies. Here we report a precise measurement of this clustering, using the redshifts of more than 141,000 galaxies from the two-degree-field (2dF) galaxy redshift survey. We determine the parameter beta = Omega0.6/b = 0.43 +/- 0.07, where Omega is the total mass-density parameter of the Universe and b is a measure of the 'bias' of the luminous galaxies in the survey. (Bias is the difference between the clustering of visible galaxies and of the total mass, most of which is dark.) Combined with the anisotropy of the cosmic microwave background, our results favour a low-density Universe with Omega approximately 0.3.