Document Detail


Mutations of the cystic fibrosis gene in patients with bronchiectasis associated with rheumatoid arthritis.
MedLine Citation:
PMID:  21131649     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: In cystic fibrosis, mutations of the CFTR gene lead to diffuse bronchiectasis (DB). DB is also associated with other diseases including rheumatoid arthritis (RA) in which the role of genetic factors in the predisposition to DB remains unclear.
METHODS: A family-based association study was carried out to determine whether the frequency of CFTR mutations was higher in patients with RA-associated DB and to determine whether a causal relationship could be established between the variant and the disease by evaluating its cosegregation with DB within families. Families of probands with RA-DB were included if one first-degree relative had RA and/or DB. The controls comprised healthy subjects requesting genetic counselling because their partner had cystic fibrosis.
RESULTS: The frequency of CFTR mutations was higher in family members with RA-DB or DB only than in unaffected relatives (p<0.005 for each comparison) and in unrelated healthy controls (p<0.001 for each comparison) but not in family members with RA only. CFTR mutations were more frequent in family members with RA-DB than in those with RA only (OR 5.30, 95% CI 2.48 to 11.33; p<5×10(-5)). They cosegregated with RA-DB in the families (sib-TDT=10.82, p=0.005).
CONCLUSIONS: RA-DB should be added to the list of phenotypes in which CFTR mutations are pathogenic. CFTR mutation is the first genetic defect linked to an extra-articular feature of RA to be described. CFTR mutations in patients with RA appear to be an important marker of the risk of associated DB, which has been linked to a less favourable prognosis.
Authors:
Xavier Puéchal; Thierry Bienvenu; Emmanuelle Génin; Jean-Marie Berthelot; Jean Sibilia; Philippe Gaudin; Christian Marcelli; Sandra Lasbleiz; Laëtitia Michou; François Cornélis; André Kahan; Daniel J Dusser
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-12-03
Journal Detail:
Title:  Annals of the rheumatic diseases     Volume:  70     ISSN:  1468-2060     ISO Abbreviation:  Ann. Rheum. Dis.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-04     Completed Date:  2011-04-21     Revised Date:  2011-06-01    
Medline Journal Info:
Nlm Unique ID:  0372355     Medline TA:  Ann Rheum Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  653-9     Citation Subset:  IM    
Affiliation:
Center for Rare Systemic Auto-immune Diseases, Department of Rheumatology, Centre Hospitalier du Mans, 194 avenue Rubillard, 72000 Le Mans, France. xpuechal@ch-lemans.fr
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MeSH Terms
Descriptor/Qualifier:
Arthritis, Rheumatoid / complications,  genetics*
Bronchiectasis / etiology,  genetics*
Case-Control Studies
Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
Female
Gene Frequency
Genetic Association Studies / methods
Genetic Linkage
Genetic Predisposition to Disease
Genotype
Humans
Mutation*
Phenotype
Chemical
Reg. No./Substance:
126880-72-6/Cystic Fibrosis Transmembrane Conductance Regulator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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