Randomized Controlled Trial

. 2020 Oct;50(5):963-967.

doi: 10.1016/j.semarthrit.2020.06.003. Epub 2020 Jun 16.

The MUC5B promoter variant does not predict progression of interstitial lung disease in systemic sclerosis

Affiliations

¹ Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, USA. Electronic address: evolkmann@mednet.ucla.edu.
² Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, USA.
³ McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, USA.
⁴ Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, USA; Department of Biostatistics, University of California, Los Angeles, Fielding School of Public Health Los Angeles, USA.
⁵ Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, USA.
⁶ Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, USA; Department of Medicine, University of Washington, Seattle, USA; Department of Rheumatology, University of Florence, Florence, Italy.
⁷ Department of Medicine, University of Michigan Medical School, Ann Arbor, USA.
⁸ Department of Biomathematics, University of California, Los Angeles, USA.

PMID: 32906032
PMCID: PMC7584725
DOI: 10.1016/j.semarthrit.2020.06.003

Randomized Controlled Trial

The MUC5B promoter variant does not predict progression of interstitial lung disease in systemic sclerosis

Elizabeth R Volkmann et al. Semin Arthritis Rheum. 2020 Oct.

. 2020 Oct;50(5):963-967.

doi: 10.1016/j.semarthrit.2020.06.003. Epub 2020 Jun 16.

Authors

Affiliations

¹ Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, USA. Electronic address: evolkmann@mednet.ucla.edu.
² Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, USA.
³ McGovern Medical School at the University of Texas Health Science Center at Houston, Houston, TX, USA.
⁴ Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, USA; Department of Biostatistics, University of California, Los Angeles, Fielding School of Public Health Los Angeles, USA.
⁵ Department of Radiology, University of California, Los Angeles, David Geffen School of Medicine, Los Angeles, USA.
⁶ Department of Medicine, University of California, Los Angeles, David Geffen School of Medicine, USA; Department of Medicine, University of Washington, Seattle, USA; Department of Rheumatology, University of Florence, Florence, Italy.
⁷ Department of Medicine, University of Michigan Medical School, Ann Arbor, USA.
⁸ Department of Biomathematics, University of California, Los Angeles, USA.

PMID: 32906032
PMCID: PMC7584725
DOI: 10.1016/j.semarthrit.2020.06.003

Abstract

Objective: To investigate the prevalence of the MUC5B promoter variant rs35705950 in patients with systemic sclerosis-interstitial lung disease (SSc-ILD) and whether its presence predicts response to immunosuppression with cyclophosphamide (CYC) and mycophenolate (MMF).

Methods: SSc-ILD patients who participated in Scleroderma Lung Study (SLS) II (MMF versus CYC) were included in this study (N = 142). TaqMan Genotyping Assays were used to determine the MUC5B rs35705950 single nucleotide polymorphism. Joint models were created to examine how the presence of this variant affected the course of the forced vital capacity (FVC) over 2 years. Linear regression models were used to investigate the relationship between the presence of this variant and the change in quantitative radiographic fibrosis.

Results: Among 128 participants who were tested for this variant, 18% possessed at least one copy of the MUC5B minor allele. Patients with at least one copy of this allele were similar to those without the allele with respect to age, sex, SSc subtype, ILD disease severity; however, this variant was rare among African Americans (3.7%). The presence of the MUC5B variant did not affect the course of the FVC, nor the change in quantitative radiographic fibrosis, ground glass or ILD scores in either treatment arm.

Conclusion: In the context of a randomized controlled trial for SSc-ILD, the presence of the MUC5B variant did not predict disease severity, nor affect treatment response to MMF or CYC. Future studies are needed to determine whether this variant affects ILD progression in other SSc cohorts and in patients receiving anti-fibrotic therapy.

Keywords: Biomarkers; Cyclophosphamide; Genetics; Interstitial lung disease; Mycophenolate mofetil; Polymorphism; Systemic sclerosis.

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Conflict of interest statement

Declaration of Competing Interests No non-financial conflicts of interest exist for any of the authors.

Figures

**Figure 1.**
Course of the FVC%-predicted from 3 to 24 months in SLS II participants with and without the MUC5B promoter variant who were randomized to CYC (A) and MMF (B). The solid line represents participants without the MUC5B promoter variant and the dotted line represents participants with the MUC5B promoter variant. The horizontal line represents the mean baseline FVC%-predicted for the entire SLS II cohort.

See this image and copyright information in PMC

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The MUC5B promoter variant does not predict progression of interstitial lung disease in systemic sclerosis

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The MUC5B promoter variant does not predict progression of interstitial lung disease in systemic sclerosis

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