FAM13A Polymorphism Is Associated With a Usual Interstitial Pneumonia Pattern in Patients With Systemic Sclerosis-Associated Interstitial Lung Disease

Authors

• Elana J Bernstein
• Francesco Boin
• Brett Elicker
• Yiming Luo
• Yawen Ren
• Meng Zhang
• John Varga
• Shervin Assassi

Language

English

Publication Date

12-1-2025

Journal

Rheumatology

DOI

10.1093/rheumatology/keae573

PMID

39418199

PMCID

PMC12695041

PubMedCentral® Posted Date

October 2024

PubMedCentral® Full Text Version

Author MSS

Abstract

Objectives: The MUC5B promoter single nucleotide polymorphism (SNP) rs35705950 has been associated with idiopathic pulmonary fibrosis (IPF) and RA-related interstitial lung disease (ILD), but not with SSc-ILD. We hypothesized that the MUC5B promoter polymorphism or other IPF susceptibility loci are associated with an increased risk for the uncommon SSc-usual interstitial pneumonia (UIP) endophenotype, rather than SSc-ILD in general.

Methods: We performed a cross-sectional study of SSc-ILD patients from four US Scleroderma Programs to investigate the frequency of MUC5B rs35705950 and 12 additional IPF susceptibility loci. SSc-ILD patients were stratified by high resolution chest CT (HRCT) imaging findings into UIP and non-UIP groups. Analysis of HRCTs performed by a thoracic radiologist blinded to participants' characteristics classified each scan as definite UIP, probable UIP, indeterminate or alternative diagnosis, according to American Thoracic Society criteria.

Results: Four-hundred and eighty-nine SSc-ILD patients were included; 80% were female and 75% were White. Twenty-three (4.7%) patients had a definite UIP pattern. The MUC5B SNP rs35705950 was not associated with a definite UIP pattern in SSc-ILD. In contrast, patients carrying two copies of the IPF risk gene FAM13A minor allele rs2609255 had significantly higher odds of a definite UIP pattern compared with the other patterns (odds ratio 3.40, 95% CI 1.19-9.70), and compared with an alternative diagnosis (odds ratio 3.65, 95% CI 1.25-10.65).

Conclusion: We demonstrated a novel association between FAM13A and SSc-UIP. Contrary to IPF and RA-ILD, the MUC5B promoter polymorphism was not associated with a definite UIP pattern in SSc-ILD.

Keywords

Humans, Female, Male, Lung Diseases, Interstitial, Scleroderma, Systemic, Mucin-5B, Middle Aged, Polymorphism, Single Nucleotide, Cross-Sectional Studies, Aged, Genetic Predisposition to Disease, GTPase-Activating Proteins, Tomography, X-Ray Computed, Idiopathic Pulmonary Fibrosis, Promoter Regions, Genetic

Published Open-Access

yes

Recommended Citation

Bernstein, Elana J; Boin, Francesco; Elicker, Brett; et al., "FAM13A Polymorphism Is Associated With a Usual Interstitial Pneumonia Pattern in Patients With Systemic Sclerosis-Associated Interstitial Lung Disease" (2025). Faculty, Staff and Student Publications. 3541.
https://digitalcommons.library.tmc.edu/uthmed_docs/3541