Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7241
pubmed:dateCreated
2009-4-27
pubmed:abstractText
Lung disease is the major cause of morbidity and mortality in cystic fibrosis, an autosomal recessive disease caused by mutations in CFTR. In cystic fibrosis, chronic infection and dysregulated neutrophilic inflammation lead to progressive airway destruction. The severity of cystic fibrosis lung disease has considerable heritability, independent of CFTR genotype. To identify genetic modifiers, here we performed a genome-wide single nucleotide polymorphism scan in one cohort of cystic fibrosis patients, replicating top candidates in an independent cohort. This approach identified IFRD1 as a modifier of cystic fibrosis lung disease severity. IFRD1 is a histone-deacetylase-dependent transcriptional co-regulator expressed during terminal neutrophil differentiation. Neutrophils, but not macrophages, from Ifrd1-deficient mice showed blunted effector function, associated with decreased NF-kappaB p65 transactivation. In vivo, IFRD1 deficiency caused delayed bacterial clearance from the airway, but also less inflammation and disease-a phenotype primarily dependent on haematopoietic cell expression, or lack of expression, of IFRD1. In humans, IFRD1 polymorphisms were significantly associated with variation in neutrophil effector function. These data indicate that IFRD1 modulates the pathogenesis of cystic fibrosis lung disease through the regulation of neutrophil effector function.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-10545485, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-10631157, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-11398102, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-11731797, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-11754464, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-11934713, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-12198164, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-12560239, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-12932353, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-15034576, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-15060170, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-15170212, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-15223861, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-15514007, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-15677751, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-15852007, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-15947021, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-16207846, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-16255782, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-16407283, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-16467360, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-16858011, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-16880254, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-17057720, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-17332481, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-17572673, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-17634072, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-18563170, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-18818360, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-19079049, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-19673948, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-9012825, http://linkedlifedata.com/resource/pubmed/commentcorrection/19242412-9831400
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
458
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1039-42
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
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