Mutations of the Cystic Fibrosis Gene in Patients with Bronchiectasis Associated with Rheumatoid Arthritis

Xavier Puéchal (1, 2, 3) , Thierry Bienvenu (4) , Emmanuelle Genin (5) , Jean-Marie Berthelot (6) , Jean Sibilia (7, 8) , Philippe Gaudin (9, 10) , Christian Marcelli (11, 12) , Sandra Lasbleiz (3, 13, 14) , Laëtitia Michou (14) , François Cornélis (14) , André Kahan (1, 2) , Daniel J Dusser (15)

1 Service de rhumatologie [CHU Cochin]
2 UPD5 - Université Paris Descartes - Paris 5
3 Centre Hospitalier Le Mans (CH Le Mans)
4 Service de biochimie et de génétique moléculaire [CHU Cochin]
5 Laboratoire Charles Friedel
6 Service de rhumatologie [Nantes]
7 Physiopathologie des arthrites
8 Hôpital de Hautepierre [Strasbourg]
9 Hôpital Michallon
10 GREPI - Groupe de Recherche et d’Étude du Processus Inflammatoire
11 Service de Rhumatologie [CHU Caen]
12 Hôpital Côte de Nacre [CHU Caen]
13 Université Paris Diderot, Sorbonne Paris Cité, Paris, France
14 GenHotel - Laboratoire de recherche européen pour la polyarthrite rhumatoïde
15 AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris]

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.

Domaines: Génétique humaine

Xavier Puéchal, Thierry Bienvenu, Emmanuelle Genin, Jean-Marie Berthelot, Jean Sibilia, et al.. Mutations of the Cystic Fibrosis Gene in Patients with Bronchiectasis Associated with Rheumatoid Arthritis. Annals of the Rheumatic Diseases, 2011, 70 (4), pp.653--659. ⟨10.1136/ard.2010.142760⟩. ⟨hal-02084404⟩