http://www.cnr.it/ontology/cnr/individuo/prodotto/ID37216
IRAK-M Is Involved in the Pathogenesis of Early-Onset Persistent Asthma (Articolo in rivista)
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- Label
- IRAK-M Is Involved in the Pathogenesis of Early-Onset Persistent Asthma (Articolo in rivista) (literal)
- Anno
- 2007-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
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- Lenuta Balaci;* Maria Cristina Spada;* Nazario Olla; Gabriella Sole; Laura Loddo; Francesca Anedda; Silvia Naitza; Maria Antonietta Zuncheddu; Andrea Maschio; Daniele Altea; Manuela Uda; Sabrina Pilia; Serena Sanna; Marco Masala; Laura Crisponi; Matilde Fattori; Marcella Devoto; Silvia Doratiotto; Stefania Rassu; Simonetta Mereu; Enrico Giua; Natalina Graziella Cadeddu; Roberto Atzeni; Umberto Pelosi; Adriano Corrias; Roberto Perra; Pier Luigi Torrazza; Pietro Pirina;
Francesco Ginesu; Silvano Marcias; Maria Grazia Schintu; Gennaro Sergio Del Giacco; Paolo Emilio Manconi; Giovanni Malerba; Andrea Bisognin; Elisabetta Trabetti; Attilio Boner;Lydia Pescollderungg; Pier Franco Pignatti; David Schlessinger; Antonio Cao; Giuseppe Pilia+ (literal)
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- PubMe (literal)
- ISI Web of Science (WOS) (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
- Lenuta Balaci;* Maria Cristina Spada;* Nazario Olla; Gabriella Sole; Laura Loddo; Francesca Anedda; Silvia Naitza; Maria Antonietta Zuncheddu; Andrea Maschio; Daniele Altea; Manuela Uda; Sabrina Pilia; Serena Sanna; Marco Masala; Laura Crisponi; Matilde Fattori: Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche (literal)
- Titolo
- IRAK-M Is Involved in the Pathogenesis of Early-Onset Persistent Asthma (literal)
- Abstract
- Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and
1100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-
24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma
susceptibility genes. We performed linkage and association analyses by transmission/disequilibrium test and case-control
analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of
pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the
study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected
significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed
that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and
replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including in-
activating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly
expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma.
IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF-kB and inflammation.
Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflam-
mation and indicate IRAK-M as a potential target for therapeutic intervention against asthma. (literal)
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