IL4R alpha mutations are associated with asthma exacerbations and mast cell/IgE expression.
Am J Respir Crit Care Med
; 175(6): 570-6, 2007 Mar 15.
Article
em En
| MEDLINE
| ID: mdl-17170387
ABSTRACT
BACKGROUND:
Severe asthma has been associated with severe exacerbations, lower lung function and greater tissue inflammation. Previous studies have suggested that mutations in interleukin-4 receptor alpha (IL4Ralpha) are associated with lower lung function, higher IgE, and a gain in receptor function. However, an effect on exacerbations and tissue inflammation has not been shown.HYPOTHESIS:
Allelic substitutions in IL4Ralpha are associated with asthma exacerbations, lower lung function, and tissue inflammation, in particular to mast cells and IgE.METHODS:
Two well-characterized cohorts of subjects with severe asthma were analyzed for five single nucleotide polymorphisms (SNPs) in IL4Ralpha. These polymorphisms were compared with the history of severe asthma exacerbations and lung function. In the primary (National Jewish) cohort, these polymorphisms were also compared with endobronchial tissue inflammatory cells and local IgE.RESULTS:
In both cohorts, the presence of the minor alleles at E375A and Q551R, which were more common in African Americans, was associated with a history of severe exacerbations and lower lung function. In the National Jewish cohort, the C allele at E375A was associated with higher tissue mast cells and higher levels of IgE bound to mast cells. The significance for most of these associations remained when whites (the larger racial subgroup) were analyzed separately.CONCLUSIONS:
SNPs in IL4Ralpha, which are more common in African Americans, are associated with severe asthma exacerbations, lower lung function, and increased mast cell-related tissue inflammation. Further studies of the impact of these mutations in African Americans and on receptor function are indicated.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Etiology_studies
/
Incidence_studies
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Observational_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2007
Tipo de documento:
Article