The<i>MUC5B</i>promoter polymorphism is associated with specific interstitial lung abnormality subtypes

Abstract

The <i>MUC5B</i> promoter polymorphism (rs35705950) has been associated with interstitial lung abnormalities (ILA) in white participants from the general population; whether these findings are replicated and influenced by the ILA subtype is not known. We evaluated the associations between the <i>MUC5B</i> genotype and ILA in cohorts with extensive imaging characterisation.We performed ILA phenotyping and <i>MUC5B</i> promoter genotyping in 5308 and 9292 participants from the AGES-Reykjavik and COPDGene cohorts, respectively.We found that ILA was present in 7% of participants from the AGES-Reykjavik, 8% of non-Hispanic white participants from COPDGene and 7% of African-American participants from COPDGene. Although the <i>MUC5B</i> genotype was strongly associated (after correction for multiple testing) with ILA (OR 2.1, 95% CI 1.8-2.4, p=1×10^-26), there was evidence of significant heterogeneity between cohorts (I²=81%). When narrowed to specific radiologic subtypes, (<i>e.g.</i> subpleural ILA), the <i>MUC5B</i> genotype remained strongly associated (OR 2.6, 95% CI 2.2-3.1, p=1×10^-30) with minimal heterogeneity (I²=0%). Although there was no evidence that the <i>MUC5B</i> genotype influenced survival, there was evidence that <i>MUC5B</i> genotype improved risk prediction for possible usual interstitial pneumonia (UIP) or a UIP pattern in non-Hispanic white populations.The <i>MUC5B</i> promoter polymorphism is strongly associated with ILA and specific radiologic subtypes of ILA, with varying degrees of heterogeneity in the underlying populations.