Asunto(s)
Celulitis (Flemón)/complicaciones , Eosinofilia/complicaciones , Leucemia Mielógena Crónica BCR-ABL Positiva/complicaciones , Piel/patología , Antineoplásicos/administración & dosificación , Biopsia , Celulitis (Flemón)/patología , Eosinofilia/patología , Proteínas de Fusión bcr-abl/genética , Humanos , Hibridación Fluorescente in Situ , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Piel/efectos de los fármacos , Resultado del TratamientoAsunto(s)
Hiperqueratosis Epidermolítica/genética , Queratodermia Palmoplantar/genética , Secuencias de Aminoácidos/genética , Contractura/genética , Humanos , Hiperqueratosis Epidermolítica/complicaciones , Queratina-1/genética , Queratodermia Palmoplantar/complicaciones , Masculino , Persona de Mediana Edad , Mutación MissenseAsunto(s)
Pueblo Asiatico/genética , Asma/genética , Dermatitis Atópica/genética , Proteínas de Filamentos Intermediarios/genética , Adolescente , Adulto , Anciano , Pueblo Asiatico/estadística & datos numéricos , Asma/etnología , Dermatitis Atópica/etnología , Proteínas Filagrina , Predisposición Genética a la Enfermedad/etnología , Humanos , Persona de Mediana Edad , Adulto JovenAsunto(s)
Dermatitis Atópica/etnología , Dermatitis Atópica/genética , Ictiosis Vulgar/etnología , Ictiosis Vulgar/genética , Proteínas de Filamentos Intermediarios/genética , Mutación/genética , Estudios de Casos y Controles , Proteínas Filagrina , Humanos , Lactante , Masculino , Linaje , PrevalenciaRESUMEN
Mutations in the gene-encoding filaggrin (FLG), a key molecule involved in skin barrier function, have been shown to be a major predisposing factor for atopic dermatitis (AD; eczema). To elucidate the pathomechanisms underlying filaggrin-related AD, we investigated stratum corneum (SC) hydration and transepidermal water loss (TEWL) as parameters of barrier function in AD patients harboring FLG mutations compared to AD patients without any FLG mutation. In filaggrin-related AD, SC hydration was both significantly reduced (P<0.01-0.05) and thicker (P<0.01-0.05) than that in healthy controls. TEWL was demonstrably increased in non-filaggrin AD compared to healthy controls (P<0.01-0.05). The objective score of atopic dermatitis (OSCORAD), a disease clinical severity index, significantly correlated with TEWL (r=0.81, P<0.005), SC hydration (r=-0.65, P<0.05), and SC thickness (r=0.59, P<0.05) in filaggrin-related AD. On the contrary, there was no correlation between these parameters and the OSCORAD in non-filaggrin AD. Furthermore, a significant correlation was obtained between the OSCORAD and specific IgE for house dust (r=0.66, P<0.05), mite allergen (r=0.53, P<0.05), and cat dander (r=0.64, P<0.05) in filaggrin-related AD, but not in non-filaggrin AD. All these data suggest that experimentally demonstrable skin barrier defects due to FLG mutations may play a crucial role in the pathogenesis of AD.
Asunto(s)
Eccema/metabolismo , Epidermis/metabolismo , Proteínas de Filamentos Intermediarios/química , Proteínas de Filamentos Intermediarios/metabolismo , Mutación , Adolescente , Adulto , Animales , Estudios de Casos y Controles , Niño , Femenino , Proteínas Filagrina , Genotipo , Humanos , Inmunoglobulina E/metabolismo , Masculino , RatonesAsunto(s)
Pérdida Auditiva Sensorineural , Ictiosis , Queratitis , Femenino , Humanos , Persona de Mediana Edad , SíndromeRESUMEN
Mutations in the gene encoding filaggrin (FLG) have been identified as the cause of ichthyosis vulgaris (IV) and shown to be major predisposing factors for atopic dermatitis (AD). However, these studies have been mainly carried out in European populations. In early 2007, we identified two Oriental-specific FLG mutations in four Japanese families with IV and reported that filaggrin mutations were also significant predisposing factors for AD in Japan. However, the frequency of FLG mutations observed in our Japanese AD cohort (5.6%), was much lower than that seen in Europeans (up to 48%). Here, we studied a further seven Japanese families with IV and identified two additional nonsense mutations in FLG, S2889X, and S3296X. We found that more than 20% of patients in our Japanese AD case series carry FLG mutations, and there is significant statistical association between the four mutations and AD (chi(2) P=8.4 x 10(-6); heterozygote odds ratio 7.57, 95% CI 2.84-23.03). These data emphasize that skin-barrier impairment due to reduced filaggrin expression plays an important role in the pathogenesis of AD and sheds further light on the genetic architecture of atopy in Japan.
