BACKGROUND AND OBJECTIVE: A common polymorphism in the MUC5B gene (rs35705950) is associated with susceptibility to idiopathic pulmonary fibrosis (IPF) and familial interstitial pneumonia (FIP). We investigated predisposition of the MUC5B polymorphism to fibrotic interstitial pneumonias in Dutch Caucasian patient cohorts. Furthermore, we investigated the correlation between MUC5B genotype and survival in these cohorts. METHODS: Sporadic IPF (spIPF, n = 115), FIP (n = 55), idiopathic non-specific interstitial pneumonia (iNSIP, n = 43), connective tissue disease associated interstitial pneumonia (CTD_IP, n = 35) and a control cohort (n = 249) were genotyped for rs35705950. RESULTS: Rs35705950 minor allele frequency (MAF) in controls was 0.09. Case-control analysis showed significant allelic association with spIPF (MAF = 0.27; P = 5.0 × 10(-10)), FIP (MAF = 0.30; P = 2.7 × 10(-9)) and iNSIP (MAF = 0.22; P = 3.4 × 10(-4)). No association was observed in CTD_IP (MAF = 0.07). FIP subgroup analysis revealed an association between MUC5B and telomerase mutated FIP (P = 0.003), and between MUC5B and FIP with unknown genetic cause (P = 1.2 × 10(-8)). In spIPF carriership of MUC5B minor allele did not influence survival. In FIP MUC5B minor allele carriers had better survival (non-carriers 37 vs carriers 53 months, P = 0.01). In iNSIP survival analysis showed an opposite effect. Worse survival was found in iNSIP patients that carried the MUC5B minor allele (non-carriers 118 vs carriers 46 months, P = 0.027) CONCLUSION: This study showed that MUC5B minor allele predisposes to spIPF, FIP and iNSIP. In spIPF, survival is not influenced by MUC5B alleles. In FIP, MUC5B minor allele predicts better survival, pointing towards a subgroup of FIP patients with a milder, MUC5B-driven form of pulmonary fibrosis.
BACKGROUND AND OBJECTIVE: A common polymorphism in the MUC5B gene (rs35705950) is associated with susceptibility to idiopathic pulmonary fibrosis (IPF) and familial interstitial pneumonia (FIP). We investigated predisposition of the MUC5B polymorphism to fibrotic interstitial pneumonias in Dutch Caucasian patient cohorts. Furthermore, we investigated the correlation between MUC5B genotype and survival in these cohorts. METHODS: Sporadic IPF (spIPF, n = 115), FIP (n = 55), idiopathic non-specific interstitial pneumonia (iNSIP, n = 43), connective tissue disease associated interstitial pneumonia (CTD_IP, n = 35) and a control cohort (n = 249) were genotyped for rs35705950. RESULTS:Rs35705950 minor allele frequency (MAF) in controls was 0.09. Case-control analysis showed significant allelic association with spIPF (MAF = 0.27; P = 5.0 × 10(-10)), FIP (MAF = 0.30; P = 2.7 × 10(-9)) and iNSIP (MAF = 0.22; P = 3.4 × 10(-4)). No association was observed in CTD_IP (MAF = 0.07). FIP subgroup analysis revealed an association between MUC5B and telomerase mutated FIP (P = 0.003), and between MUC5B and FIP with unknown genetic cause (P = 1.2 × 10(-8)). In spIPF carriership of MUC5B minor allele did not influence survival. In FIP MUC5B minor allele carriers had better survival (non-carriers 37 vs carriers 53 months, P = 0.01). In iNSIP survival analysis showed an opposite effect. Worse survival was found in iNSIP patients that carried the MUC5B minor allele (non-carriers 118 vs carriers 46 months, P = 0.027) CONCLUSION: This study showed that MUC5B minor allele predisposes to spIPF, FIP and iNSIP. In spIPF, survival is not influenced by MUC5B alleles. In FIP, MUC5B minor allele predicts better survival, pointing towards a subgroup of FIP patients with a milder, MUC5B-driven form of pulmonary fibrosis.
Authors: Chad A Newton; Justin M Oldham; Brett Ley; Vikram Anand; Ayodeji Adegunsoye; Gabrielle Liu; Kiran Batra; Jose Torrealba; Julia Kozlitina; Craig Glazer; Mary E Strek; Paul J Wolters; Imre Noth; Christine Kim Garcia Journal: Eur Respir J Date: 2019-04-11 Impact factor: 16.671
Authors: Ashley R Rackow; David J Nagel; Claire McCarthy; Jennifer Judge; Shannon Lacy; Margaret A T Freeberg; Thomas H Thatcher; R Matthew Kottmann; Patricia J Sime Journal: Eur Respir J Date: 2020-11-26 Impact factor: 16.671
Authors: Emily K Wu; Robert D Ambrosini; R Matthew Kottmann; Christopher T Ritchlin; Edward M Schwarz; Homaira Rahimi Journal: Curr Rheumatol Rev Date: 2019
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Authors: Pierre-Antoine Juge; Joyce S Lee; Esther Ebstein; Hiroshi Furukawa; Evgenia Dobrinskikh; Steven Gazal; Caroline Kannengiesser; Sébastien Ottaviani; Shomi Oka; Shigeto Tohma; Naoyuki Tsuchiya; Jorge Rojas-Serrano; Montserrat I González-Pérez; Mayra Mejía; Ivette Buendía-Roldán; Ramcés Falfán-Valencia; Enrique Ambrocio-Ortiz; Effrosyni Manali; Spyros A Papiris; Theofanis Karageorgas; Dimitrios Boumpas; Katarina Antoniou; Coline H M van Moorsel; Joanne van der Vis; Yaël A de Man; Jan C Grutters; Yaping Wang; Raphaël Borie; Lidwine Wemeau-Stervinou; Benoît Wallaert; René-Marc Flipo; Hilario Nunes; Dominique Valeyre; Nathalie Saidenberg-Kermanac'h; Marie-Christophe Boissier; Sylvain Marchand-Adam; Aline Frazier; Pascal Richette; Yannick Allanore; Jean Sibilia; Claire Dromer; Christophe Richez; Thierry Schaeverbeke; Huguette Lioté; Gabriel Thabut; Nadia Nathan; Serge Amselem; Martin Soubrier; Vincent Cottin; Annick Clément; Kevin Deane; Avram D Walts; Tasha Fingerlin; Aryeh Fischer; Jay H Ryu; Eric L Matteson; Timothy B Niewold; Deborah Assayag; Andrew Gross; Paul Wolters; Marvin I Schwarz; Michael Holers; Joshua J Solomon; Tracy Doyle; Ivan O Rosas; Cornelis Blauwendraat; Mike A Nalls; Marie-Pierre Debray; Catherine Boileau; Bruno Crestani; David A Schwartz; Philippe Dieudé Journal: N Engl J Med Date: 2018-10-20 Impact factor: 91.245
Authors: Paul J Wolters; Timothy S Blackwell; Oliver Eickelberg; James E Loyd; Naftali Kaminski; Gisli Jenkins; Toby M Maher; Maria Molina-Molina; Paul W Noble; Ganesh Raghu; Luca Richeldi; Marvin I Schwarz; Moises Selman; Wim A Wuyts; David A Schwartz Journal: Lancet Respir Med Date: 2018-02 Impact factor: 30.700