Radiological scores in IPF patients according to MUC5B polymorphism

Background: The MUC5B rs35705950 mutant T allele is the strongest genetic risk factor for familiar and sporadic IPF. In addition, carriage of the T allele has been associated with better outcomes. We sought to determine whether MUC5B rs35705950 genotype affects radiological patterns of IPF patients and how they may change during the first year of antifibrotic therapy. Methods: 78 IPF patients on antifibrotic treatment and on regular follow-up were genotyped for MUC5B rs35705950 by PCR amplification and Sanger sequencing and classified according to the carriage of the mutant T allele. HRCT patterns were quantified at treatment initiation (HRCT0) and after 1 year (HRCT1) as: ground glass opacities (Alveolar Score, AS), reticulations (Interstitial Score, IS) and honeycombing (HC). Results: 54/78 patients(69%) carried at least one copy of the T allele. At HRCT0, radiological scores were similar across the TT/TG/GG subgroups. Carriers of the T allele displayed similar FVC loss in the 1-year of treatment as GG carriers, but overall survival was longer in the TT/TG group compared to the GG group (79vs.41months, HR0.35,95%CI:0.13-0.90). In the TT/TG group, HC increased significantly [from 2(0-41)% to 5(0-50)%;p=0.001], whereas in the GG group both AS [from 16(0-44)% to 18(1-86)%;p=0.05] and HC [from 3(0-70)% to 7(0-83)%;p=0.007] increased significantly at HRCT1. Conclusions: In IPF patients carrying the MUC5B rs35705950 T allele, HC increases over time, whereas in noncarriers both HC and AS increase despite a similar FVC loss in the 1-year of treatment. Longitudinal HRCT may help in clarifying the prognostic role of MUC5B rs35705950.