The MUC5B promoter polymorphism is associated with specific interstitial lung abnormality subtypes

Area of Science:

• Genetics
• Pulmonology
• Radiology

Background:

• The MUC5B promoter polymorphism (rs35705950) is linked to interstitial lung abnormalities (ILA) in general white populations.
• Replication of these findings and their influence by ILA subtype remain unclear.

Purpose of the Study:

• Evaluate the association between MUC5B genotype and ILA in cohorts with detailed imaging.
• Investigate the impact of ILA subtypes on this association.

Main Methods:

• Phenotyped ILA and genotyped MUC5B promoter in AGES-Reykjavik (5308 participants) and COPDGene (9292 participants) cohorts.
• Analyzed associations between MUC5B genotype and ILA, including specific radiologic subtypes.

Main Results:

• MUC5B genotype strongly associated with ILA (OR 2.1, p=1x10^-26), with significant heterogeneity (I^2=81%).
• Association remained strong for subpleural ILA (OR 2.6, p=1x10^-30) with minimal heterogeneity (I^2=0%).
• MUC5B genotype improved risk prediction for possible usual interstitial pneumonia (UIP) or UIP pattern in non-Hispanic white populations, but did not influence survival.

Conclusions:

• The MUC5B promoter polymorphism is strongly associated with ILA and its radiologic subtypes.
• Population heterogeneity exists, but the association is robust for specific subtypes like subpleural ILA.
• MUC5B genotype is a valuable predictor for specific interstitial pneumonia patterns, particularly in non-Hispanic white individuals.