CT Imaging Phenotypes of Pulmonary Fibrosis in the MUC5B Promoter Site Polymorphism

Chest. 2016 May;149(5):1215-22. doi: 10.1016/j.chest.2015.11.009. Epub 2016 Jan 13.

Abstract

Background: To determine the effect of the MUC5B promoter polymorphism (rs35705950) on the CT imaging appearance of pulmonary fibrosis.

Methods: High-resolution CT scans of 1,764 subjects were scored as part of a, genomewide association study with institutional review board approval; 1,491 of these had pulmonary fibrosis on CT scans and were included in the study. Two thoracic radiologists independently scored CT scans systematically. Discrepancies were resolved by a third thoracic radiologist. All patients were genotyped specifically for the rs35705950 single-nucleotide polymorphism (SNP). Two-tailed Fisher exact or χ(2) tests and Student t tests or Mann-Whitney U tests were used to compare proportions and means, respectively.

Results: The major and minor alleles at the rs35705950 SNP are guanine (G) and thymine (T), respectively: 514 were homozygous for the major allele (G group), and 977 were heterozygous or homozygous for the minor allele (T group). The G group had a higher proportion than the T group with ground-glass opacity (62.1% vs 54.2%; P = .04). There was no significant difference between the G and T groups regarding presence of honeycombing. The T group showed a significantly higher subpleural axial distribution of fibrosis than did the G group (62.3% vs 42.2%; P < .0001). The T group showed a lower proportion of diagnoses inconsistent with usual interstitial pneumonitis (UIP; 20.3% compared with 30.5% for the G group) and a greater proportion of confident (probable UIP and UIP) UIP diagnoses (43.8% compared with 32.6% for the G group).

Conclusions: The MUC5B promoter polymorphism identifies a pattern of fibrosis that is different from other causes of fibrosis and may respond differently to potential therapies.

Keywords: CT imaging; MUC5B; idiopathic pulmonary fibrosis; rs35705950; usual interstitial pneumonitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Cohort Studies
  • Female
  • Genotype
  • Heterozygote
  • Humans
  • Idiopathic Pulmonary Fibrosis / diagnostic imaging*
  • Idiopathic Pulmonary Fibrosis / genetics
  • Lung / diagnostic imaging*
  • Male
  • Middle Aged
  • Mucin-5B / genetics*
  • Phenotype
  • Polymorphism, Genetic
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic / genetics
  • Pulmonary Fibrosis / diagnostic imaging
  • Pulmonary Fibrosis / genetics
  • Tomography, X-Ray Computed

Substances

  • MUC5B protein, human
  • Mucin-5B