RESUMEN
BACKGROUND: Polymorphisms of interleukin genes related to IgE production and inflammation are predictors of hypersensitivity to betalactam, but nothing is known on the influence of NOD genes, despite their association with inflammation and atopy. OBJECTIVE: To evaluate the association of NOD2 and NOD1 polymorphisms with betalactam allergy. METHOD: We genotyped 3 polymorphisms of NOD2 and 1 of NOD1 in 368 Italian and 387 Spanish patients, compared with 368 and 326 controls, respectively. RESULTS: CT/TT genotypes of rs2066845 of NOD2 predicted a lower risk in Italy (P = 0.003), while WT/insC genotype of rs5743293 (also in leucine-rich repeat domain) predicted a higher risk in Spain (P = 0.007). G allele of rs2066845 was associated with a higher level of IgE in the Italian population. CONCLUSION: The mirrored influence of these NOD2 polymorphisms on betalactam allergy in two populations suggests a link with pathways of inflammation and/or atopy through mechanisms, which need to be clarified.
Asunto(s)
Alérgenos/genética , Alérgenos/inmunología , Proteína Adaptadora de Señalización NOD1/genética , Proteína Adaptadora de Señalización NOD2/genética , Polimorfismo Genético/inmunología , beta-Lactamas/inmunología , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Hipersensibilidad/genética , Hipersensibilidad/inmunología , Hipersensibilidad/patología , Inmunoglobulina E/biosíntesis , Inflamación/genética , Inflamación/inmunología , Inflamación/patología , Masculino , Persona de Mediana Edad , Adulto Joven , beta-Lactamas/efectos adversosRESUMEN
BACKGROUND: Nonsynonymous polymorphisms in genes coding for histamine-metabolizing enzymes, diamine oxidase and histamine N-methyltransferase are related to the risk of developing allergic diseases. The role of polymorphisms in the histidine decarboxylase gene remains unexplored. The objective of this study is to identify novel polymorphisms in the human histidine decarboxylase gene and to analyse the clinical association of nonsynonymous polymorphisms with rhinitis. METHODS: We performed a single-strand conformational polymorphism analysis of the histidine decarboxylase gene sequence. The presence of two nonsynonymous polymorphisms Thr31Met (rs17740607) and Glu644Asp (rs2073440) was analysed in 442 unrelated patients with allergic rhinitis, 233 of whom also had asthma, and in 486 healthy subjects. RESULTS: We observed three novel polymorphisms designated as ss50402829, ss50402830 and ss50402831-(rs17740607) with allele frequencies = 0.005, 0.208 and 0.073, respectively. Statistically significant differences were observed for the histidine decarboxylase Glu644Asp (rs2073440) polymorphism, with OR (95% CI) values for homozygous carriers of the Glu644 allele equal to 3.12 (1.75-5.56, P < 0.00005) for all patients, 3.38 (1.54-7.44, P = 0.002) for patients with rhinitis alone, and 2.92 (1.43-5.95), P = 0.003 for patients with rhinitis + asthma, when compared with healthy controls. A significant Glu644 gene-dose effect was observed for overall patients (P = 0.0001), for patients with rhinitis alone (P = 0.005) and for patients with rhinitis + asthma (P = 0.010). CONCLUSIONS: The HDC allele Glu644 in homozygosity increases the risk of developing rhinitis in the studied population. This adds to increasing evidence supporting a prominent role of genetic variations related to histamine homeostasis in the risk to develop allergic diseases.
Asunto(s)
Predisposición Genética a la Enfermedad/genética , Histidina Descarboxilasa/genética , Hipersensibilidad/genética , Rinitis/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Asma/complicaciones , Asma/enzimología , Asma/genética , Niño , Preescolar , Femenino , Frecuencia de los Genes , Haplotipos , Humanos , Hipersensibilidad/enzimología , Masculino , Persona de Mediana Edad , Polimorfismo Conformacional Retorcido-Simple , Rinitis/complicaciones , Rinitis/enzimología , Adulto JovenRESUMEN
Se analizan los resultados en 1.015 pacientes hipertiroideos, I131 y cirugia. Evidenciandose que con el tratamiento quirurgico se obtiene un inmediato control del sindrome, menor recidiva, y los casos de hipotiroidismo serian inferiores a los del I131 para igual seguimiento. Se analizan los resultados del empleo, pre, intra y postoperatorio del propanolol, y se concluye que la cirugia continua siendo el tratamiento de eleccion, fundamentalmente en un area de bocio endemico