The promoter polymorphism is associated with specific interstitial lung abnormality subtypes.

The 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 genotype and ILA in cohorts with extensive imaging characterisation.We performed ILA phenotyping and 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 genotype was strongly associated (after correction for multiple testing) with ILA (OR 2.1, 95% CI 1.8-2.4, p=1×10), there was evidence of significant heterogeneity between cohorts (I=81%). When narrowed to specific radiologic subtypes, ( subpleural ILA), the genotype remained strongly associated (OR 2.6, 95% CI 2.2-3.1, p=1×10) with minimal heterogeneity (I=0%). Although there was no evidence that the genotype influenced survival, there was evidence that genotype improved risk prediction for possible usual interstitial pneumonia (UIP) or a UIP pattern in non-Hispanic white populations.The promoter polymorphism is strongly associated with ILA and specific radiologic subtypes of ILA, with varying degrees of heterogeneity in the underlying populations.