Identificazione e caratterizzazione di un gene associato all'asma ad insorgenza precoce persistente

Asthma is a multifactorial disease influenced by genetic and environmental factors. The aim of the study is to identify new susceptibility genes, using the Sardinian founder population, in which limited heterogeneity as well as of environmental conditions should facilitate the study of multifactorial traits. Asthma was diagnosed by a pulmonary physician, in accordante with American Thoracic Society criteria. We performed linkage and association analyses by transmission/disequilibrium test and case-control analysis in the candidate region 12q13-24 already implicated in asthma etiology in multiple populations We selected a cutoff age of 13 years at asthma onset, to stratify the sample and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene in the candidate region implicated in early-onset persistent asthma. We defined protective and predisposing haplotypes and replicated associations in an outbred Italian population. Sequence analysis in 100 patients found mutations in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. Here, was report that variants in the interleukin-1 receptor associated kinase-M gene are associated with early-onset persistent asthma and indicate IRAK-M as a potential new target for therapeutic intervention against asthma and atopic diseases.