RESUMEN
OBJECTIVE: Higher gluten intake, frequent gastrointestinal infections and adenovirus, enterovirus, rotavirus and reovirus have been proposed as environmental triggers for coeliac disease. However, it is not known whether an interaction exists between the ingested gluten amount and viral exposures in the development of coeliac disease. This study investigated whether distinct viral exposures alone or together with gluten increase the risk of coeliac disease autoimmunity (CDA) in genetically predisposed children. DESIGN: The Environmental Determinants of Diabetes in the Young study prospectively followed children carrying the HLA risk haplotypes DQ2 and/or DQ8 and constructed a nested case-control design. From this design, 83 CDA case-control pairs were identified. Median age of CDA was 31 months. Stool samples collected monthly up to the age of 2 years were analysed for virome composition by Illumina next-generation sequencing followed by comprehensive computational virus profiling. RESULTS: The cumulative number of stool enteroviral exposures between 1 and 2 years of age was associated with an increased risk for CDA. In addition, there was a significant interaction between cumulative stool enteroviral exposures and gluten consumption. The risk conferred by stool enteroviruses was increased in cases reporting higher gluten intake. CONCLUSIONS: Frequent exposure to enterovirus between 1 and 2 years of age was associated with increased risk of CDA. The increased risk conferred by the interaction between enteroviruses and higher gluten intake indicate a cumulative effect of these factors in the development of CDA.
Asunto(s)
Enfermedades Autoinmunes/etiología , Enfermedad Celíaca/etiología , Enterovirus/aislamiento & purificación , Heces/virología , Glútenes/administración & dosificación , Adenoviridae/aislamiento & purificación , Autoanticuerpos/sangre , Enfermedades Autoinmunes/sangre , Enfermedades Autoinmunes/genética , Autoinmunidad , Estudios de Casos y Controles , Enfermedad Celíaca/sangre , Enfermedad Celíaca/genética , Preescolar , Dieta , Femenino , Proteínas de Unión al GTP/inmunología , Predisposición Genética a la Enfermedad , Antígenos HLA-DQ/genética , Humanos , Lactante , Masculino , Metagenómica , Proteína Glutamina Gamma Glutamiltransferasa 2 , Factores de Riesgo , Transglutaminasas/inmunologíaRESUMEN
Maturity onset diabetes of the young (MODY) is a monogenic form of diabetes inherited as an autosomal dominant trait. The second most common cause is GCK-MODY due to heterozygous mutations in the GCK gene which impair the glucokinase function through different mechanisms such as enzymatic activity, protein stability, and increased interaction with its receptor. The enzyme normally acts as a glucose sensor in the pancreatic beta cell and regulates insulin secretion. We report here a three-generation nonobese family diagnosed with diabetes. All affected family members presented with mild hyperglycemia and mostly slightly elevated hemoglobin A1c values. Genetic testing revealed a novel heterozygous T â C exchange in exon 8 of the GCK gene which resulted in a phenylalanine(330) TTC â serine (TCC)/p.Phe330Ser/F330S substitution.