title: Effect of Muc5b promoter polymorphism on disease predisposition and survival in idiopathic interstitial pneumonias.
abstract: 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.affiliation: St Antonius Interstitial Lung Disease Center, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.|Department of Clinical Chemistry, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Joanne J
authors.initials: JJ
authors.lastname: van der Vis
authors.affiliation: St Antonius Interstitial Lung Disease Center, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Reinier
authors.initials: R
authors.lastname: Snetselaar
authors.affiliation: Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Karin M
authors.initials: KM
authors.lastname: Kazemier
authors.affiliation: St Antonius Interstitial Lung Disease Center, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Liesbeth
authors.initials: L
authors.lastname: ten Klooster
authors.affiliation: St Antonius Interstitial Lung Disease Center, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.|Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Grutters
authors.affiliation: St Antonius Interstitial Lung Disease Center, Department of Pulmonology, St Antonius Hospital, Nieuwegein, The Netherlands.|Division of Heart and Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Coline H M
authors.initials: CH
authors.lastname: van Moorsel
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D054988:Idiopathic Interstitial Pneumonias / Q000235:genetics* / Q000401:mortality*; D054990:Idiopathic Pulmonary Fibrosis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D055257:Mucin-5B / Q000235:genetics*; D009426:Netherlands; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics; D015996:Survival Rate; D019098:Telomerase / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D055257:Mucin-5B; D019098:Telomerase
keywords: MUC5B; familiar interstitial pneumonia; idiopathic non-specific pneumonia; idiopathic pulmonary fibrosis; survival