Chest
Volume 149, Issue 5, May 2016, Pages 1215-1222
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Original Research: Diffuse Lung Disease
CT Imaging Phenotypes of Pulmonary Fibrosis in the MUC5B Promoter Site Polymorphism

Part of this article has been presented for oral presentation at the 2013 Radiological Society of North America Annual Meeting, December 1-6, 2013, Chicago, IL.
https://doi.org/10.1016/j.chest.2015.11.009Get rights and content

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 χ2 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.

Section snippets

Materials and Methods

This case control study was approved by our institutional review board (NJH 1441A). Informed consent was obtained from all subjects.

Results

The major and minor alleles at the rs35705950 SNP are G and T, respectively. There were 514 GG (G group) and 977 GT or TT (T group) subjects. The heterozygous GT group and the homozygous TT group were combined based on the dominant allele model.21

Discussion

There is growing interest in the relationship of the rs35705950 SNP variant and pulmonary fibrosis; however, to our knowledge, no studies have systematically reported the chest CT imaging manifestations relative to this SNP.5, 7, 8, 10, 14, 22 Multiple separate studies have shown a strong association between IPF and the T minor allele.6, 7, 8, 9, 10, 11, 12, 13 The odds ratios for pulmonary fibrosis among subjects who were heterozygous and those who were homozygous for the T minor allele of

Acknowledgments

Author contributions: J. H. C. takes responsibility for (is the guarantor of) the content of the manuscript, including the data and analysis. J. H. C., A. L. P., and D. A. L. designed the study. J. L. T. coordinated the clinical evaluations. J. H. C., A. C., and D. A. L. performed radiological phenotyping of study subjects. D. F. M. managed the database. A. L. P. and T. E. F. analyzed data. A. L. P. created tables. J. H. C., A. L. P., M. I. S., D. A. S., and D. A. L. provided advice on design

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    Dr Chung is currently at The University of Chicago Medicine (Chicago, IL).

    FUNDING/SUPPORT: This research was funded by R01 HL097163 (PI D. A. Schwartz), 1I01BX001534 (D. A. Schwartz), P01 HL092870 (PD D. A. Schwartz), and R01 HL095393 (PI D.A. Schwartz).

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