Effect of <scp>M</scp>uc5b promoter polymorphism on disease predisposition and survival in idiopathic interstitial pneumonias

Abstract

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.