Association Between the MUC5B Promoter Polymorphism and Survival in Patients With Idiopathic Pulmonary Fibrosis

Main Outcomes and Measures The primary end point was all-cause mortality. Results ThenumbersofpatientsintheGG,GT,andTTgenotypegroupswere148(34%), 259 (59%), and 31 (7%), respectively, in the INSPIRE cohort and 41 (28%), 98 (66%), and9(6%),respectively,intheChicagocohort.Themedianfollow-upperiodwas1.6years for INSPIRE and 2.1 years for Chicago. During follow-up, there were 73 deaths (36 GG, 35GT,and2TT)amongINSPIREpatientsand64deaths(26GG,36GT,and2TT)among Chicagopatients.Theunadjusted2-yearcumulativeincidenceofdeathwasloweramong patientscarrying1ormorecopiesoftheIPFriskallele(T)inboththeINSPIREcohort(0.25 [95% CI, 0.17-0.32] for GG, 0.17 [95% CI, 0.11-0.23] for GT, and 0.03 [95% CI, 0.000.09] for TT) and the Chicago cohort (0.50 [95% CI, 0.31-0.63] for GG, 0.22 [95% CI, 0.13-0.31] for GT, and 0.11 [95% CI, 0.00-0.28] for TT). In the INSPIRE cohort, the TT andGTgenotypes(riskforIPF)wereassociatedwithimprovedsurvivalcomparedwithGG (hazardratios,0.23[95%CI,0.10-0.52]and0.48[95%CI,0.31-0.72],respectively;P.001). ThisfindingwasreplicatedintheChicagocohort(hazardratios,0.15[95%CI,0.05-0.49] and0.39[95%CI,0.21-0.70],respectively;P.002).TheobservedassociationofMUC5B withsurvivalwasindependentofage,sex,forcedvitalcapacity,diffusingcapacityofcarbon monoxide, MMP-7, and treatment status. The addition of the MUC5B genotype to the survivalmodelssignificantlyimprovedthepredictiveaccuracyofthemodelinboththeINSPIRE cohort (C=0.71 [95% CI, 0.64-0.75] vs C=0.68 [95% CI, 0.61-0.73]; P.001) and the Chicago cohort (C=0.73 [95% CI, 0.62-0.78] vs C=0.69 [95% CI, 0.59-0.75]; P=.01). ConclusionsandRelevance AmongpatientswithIPF,acommonriskpolymorphism in MUC5B was significantly associated with improved survival. Further research is necessarytorefinetheriskestimatesandtodeterminetheclinicalimplicationsofthesefindings.