RESUMEN
BACKGROUND: Common polymorphisms have been identified in genes suspected to play a role in asthma. We investigated their associations with wheeze and allergy in a case-control sample from Phase 2 of the International Study of Asthma and Allergies in Childhood. METHODS: We compared 1105 wheezing and 3137 non-wheezing children aged 8-12 years from 17 study centres in 13 countries. Genotyping of 55 candidate single nucleotide polymorphisms (SNPs) in 14 genes was performed using the Sequenom System. Logistic regression models were fitted separately for each centre and each SNP. A combined per allele odds ratio and measures of heterogeneity between centres were derived by random effects meta-analysis. RESULTS: Significant associations with wheeze in the past year were detected in only four genes (IL4R, TLR4, MS4A2, TLR9, P<0.05), with per allele odds ratios generally <1.3. Variants in IL4R and TLR4 were also related to allergen-specific IgE, while polymorphisms in FCER1B (MS4A2) and TLR9 were not. There were also highly significant associations (P<0.001) between SPINK5 variants and visible eczema (but not IgE levels) and between IL13 variants and total IgE. Heterogeneity of effects across centres was rare, despite differences in allele frequencies. CONCLUSIONS: Despite the biological plausibility of IgE-related mechanisms in asthma, very few of the tested candidates showed evidence of association with both wheeze and increased IgE levels. We were unable to confirm associations of the positional candidates DPP10 and PHF11 with wheeze, although our study had ample power to detect the expected associations of IL13 variants with IgE and SPINK5 variants with eczema.
Asunto(s)
Estudios de Asociación Genética , Hipersensibilidad/genética , Ruidos Respiratorios/genética , Alérgenos/inmunología , Asia , Asma/genética , Niño , Proteínas de Unión al ADN/genética , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/genética , Ecuador , Eccema/genética , Europa (Continente) , Frecuencia de los Genes/genética , Factores de Intercambio de Guanina Nucleótido/genética , Humanos , Hipersensibilidad/sangre , Hipersensibilidad/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Interleucina-13/genética , Subunidad alfa del Receptor de Interleucina-4/genética , Desequilibrio de Ligamiento/genética , Receptores de Lipopolisacáridos/genética , Nueva Zelanda , Polimorfismo de Nucleótido Simple/genética , Proteínas Inhibidoras de Proteinasas Secretoras/genética , Receptores de IgE/genética , Ruidos Respiratorios/inmunología , Rinitis Alérgica Perenne/genética , Rinitis Alérgica Estacional/genética , Inhibidor de Serinpeptidasas Tipo Kazal-5 , Pruebas Cutáneas , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genética , Receptor Toll-Like 9/genética , Factores de Transcripción/genética , Factor de Crecimiento Transformador beta1/genética , Factor de Necrosis Tumoral alfa/genéticaRESUMEN
Biovarieties of M. tuberculosis were studied in 736 isolates. Most of them were classified into the well known varieties but two were considered as new varieties nominated H and I. Variety H has valine and cystine aminopeptidases, is active also against trypine, and contains alpha glucosides. Variety I contains the enzymes plus alfa glucosidase.