Asunto(s)
Dermatitis Atópica/epidemiología , Dermatitis Atópica/genética , Proteínas de Filamentos Intermediarios/genética , Crema para la Piel/administración & dosificación , Piel/microbiología , Estudios de Casos y Controles , Dermatitis Atópica/prevención & control , Femenino , Proteínas Filagrina , Heterocigoto , Humanos , Lactante , Japón/epidemiología , Masculino , Mutación , Prevalencia , Staphylococcus aureus/aislamiento & purificación , Pérdida Insensible de Agua/efectos de los fármacosAsunto(s)
Predisposición Genética a la Enfermedad/genética , Hipersensibilidad/genética , Proteínas de Filamentos Intermediarios/genética , Adulto , Alérgenos/inmunología , Pueblo Asiatico/genética , Femenino , Proteínas Filagrina , Humanos , Inmunoglobulina E/sangre , Masculino , Mutación , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido SimpleAsunto(s)
Dermatitis Atópica/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Proteína smad3/genética , Animales , Pueblo Asiatico/genética , Estudios de Casos y Controles , Dermatitis Atópica/inmunología , Genotipo , Humanos , Japón , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/metabolismo , Ratones , Polimorfismo de Nucleótido Simple/inmunología , Proteína smad3/inmunologíaRESUMEN
Filaggrin (FLG) plays an important role in the barrier function of the skin. Several loss-of-function mutations in the FLG gene have been identified in patients with ichthyosis vulgaris, and these null mutations are associated with atopic dermatitis (AD) development. In this study, we examined tag single nucleotide polymorphisms (tSNPs) and null mutations in FLG for possible associations with AD and atopic phenotypes in a Japanese population. Transmission disequilibrium test of 105 AD families showed that the null allele of the S2554X variant of FLG tended to be overtransmitted to AD-affected offspring; however, the P value did not reach statistical significance. In a case-control comparison of 376 AD cases and 923 nonallergic controls, the null allele of S2554X was significantly associated with AD (P = 0.0012), and the association was strengthened in subjects with AD alone (P = 0.000024). We found that 3321delA and S2554X were also associated with elevated levels of immunoglobulin E (IgE). Combined null mutation carriers were observed more in AD patients and in subjects with high IgE than in control subjects. The combined P value for the family and case-control data was significant for the S2554X and combined null mutations. Our data further support the importance of FLG in AD development.
Asunto(s)
Dermatitis Atópica/genética , Inmunoglobulina E/biosíntesis , Proteínas de Filamentos Intermediarios/genética , Mutación/genética , Adolescente , Adulto , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Niño , Preescolar , Enfermedad Crónica , Codón sin Sentido , Dermatitis Atópica/inmunología , Dermatitis Atópica/metabolismo , Proteínas Filagrina , Humanos , Inmunoglobulina E/sangre , Lactante , Proteínas de Filamentos Intermediarios/deficiencia , Proteínas de Filamentos Intermediarios/fisiología , Persona de Mediana EdadRESUMEN
BACKGROUND: Atopic dermatitis develops as a result of complex interactions between several genetic and environmental factors. To date, 4 genome-wide linkage studies of atopic dermatitis have been performed in Caucasian populations, however, similar studies have not been done in Asian populations. The aim of this study was to identify chromosome regions linked to atopic dermatitis in a Japanese population. METHODS: We used a high-density, single nucleotide polymorphism genotyping assay, the Illumina BeadArray Linkage Mapping Panel (version 4) comprising 5,861 single nucleotide polymorphisms, to perform a genome-wide linkage analysis of 77 Japanese families with 111 affected sib-pairs with atopic dermatitis. RESULTS: We found suggestive evidence for linkage with 15q21 (LOD = 2.01, NPL = 2.87, P = .0012) and weak linkage to 1q24 (LOD = 1.26, NPL = 2.44, P = .008). CONCLUSION: We report the first genome-wide linkage study of atopic dermatitis in an Asian population, and novel loci on chromosomes 15q21 and 1q24 linked to atopic dermatitis. Identification of novel causative genes for atopic dermatitis will advance our understanding of the pathogenesis of atopic dermatitis.
Asunto(s)
Pueblo Asiatico/genética , Dermatitis Atópica/etnología , Dermatitis Atópica/genética , Genómica , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Salud de la Familia , Femenino , Humanos , Escala de Lod , Masculino , Persona de Mediana EdadRESUMEN
A rare case of Stevens-Johnson syndrome (SJS) due to peplomycin in a 48-year-old man is described. The patient had squamous cell carcinoma on the scalp and underwent preoperative neoadjuvant chemotherapy with peplomycin. On the fifth day of the chemotherapy, he developed a fever and multiple dusky violaceous erythematous areas and pustules on his trunk, thighs, and palms. Erosive erythema and erosions also developed on his soles, scrotum, and oral mucosa. A biopsy specimen taken from the eruption on the thigh revealed marked liquefaction degeneration of the basal layer of the epidermis. Laboratory examinations demonstrated aggravation of liver function. Additionally, the patient developed conjunctivitis and corneal erosions. Although he had some subcorneal pustules, we diagnosed the case as an unusual form of SJS because of severe mucous membrane involvement. Oral prednisolone was administered, and the symptoms subsided. Then the patient underwent wide local excision. One month after surgery, we performed patch tests and a lymphocyte stimulation test with negative results. Then we re-administered peplomycin starting with 1/20 of a daily dose and gradually increasing the dose each day. After administration of the regular daily dose, the patient had a relapse of fever, eruptions, stomatitis, corneal erosions, and liver dysfunction. Therefore, a definite diagnosis of drug eruption due to peplomycin was made.
