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Effect of M uc5b promoter polymorphism on disease predisposition and survival in idiopathic interstitial pneumonias
Author(s) -
Vis Joanne J.,
Snetselaar Reinier,
Kazemier Karin M.,
Klooster Liesbeth,
Grutters Jan C.,
Moorsel Coline H.M.
Publication year - 2016
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/resp.12728
Subject(s) - medicine , genetic predisposition , disease , polymorphism (computer science) , idiopathic interstitial pneumonia , usual interstitial pneumonia , interstitial lung disease , genetics , pathology , genotype , gene , lung , biology
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.