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Updated: May 23, 2026
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Native Polyacrylamide Gel Electrophoresis Immunoblot Analysis of Endogenous IRF5 Dimerization
Published on: October 6, 2019
IRF5 polymorphism predicts prognosis in patients with systemic sclerosis
Roozbeh Sharif1, Maureen D Mayes, Filemon K Tan
1Division of Rheumatology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
Annals of the Rheumatic Diseases
|March 24, 2012
Summary
A specific gene variant (IRF5 rs4728142) in systemic sclerosis (SSc) is linked to better survival and less severe lung disease. This finding may help predict patient outcomes and understand SSc progression.
Area of Science:
- Genetics
- Immunology
- Rheumatology
Background:
- Systemic sclerosis (SSc) is a complex autoimmune disease with significant morbidity and mortality.
- Previous genome-wide association studies (GWAS) identified non-major histocompatibility complex (MHC) susceptibility loci for SSc.
- The impact of these genetic variants on SSc clinical outcomes, such as survival and interstitial lung disease (ILD) severity, requires further investigation.
Purpose of the Study:
- To investigate the association between specific gene variants identified in a GWAS and survival in patients with SSc.
- To determine if these gene variants influence the severity of interstitial lung disease (ILD) in SSc patients.
- To explore the functional relevance of identified single nucleotide polymorphisms (SNPs) in SSc.
Main Methods:
- A cohort of 1443 Caucasian SSc patients from the Genetics versus Environment In Scleroderma Outcome Study (GENISOS) and the Scleroderma Family Registry, with a replication cohort from The Johns Hopkins Scleroderma Cohort, were analyzed.
- Forced vital capacity (FVC)% predicted was used as a measure of ILD severity.
- Five significant SNPs, including IRF5 (rs10488631, rs12537284, rs4728142), STAT4 (rs3821236), and CD247 (rs2056626), were examined.
Main Results:
- The IRF5 rs4728142 minor allele was significantly associated with longer survival in both discovery and replication cohorts (HR: 0.75, p = 0.002).
- This association remained significant and independent of established prognostic factors like age at onset, disease type, and autoantibody profile.
- The IRF5 rs4728142 minor allele also correlated with higher FVC% predicted, indicating milder ILD, and was associated with lower IRF5 transcript expression, suggesting functional relevance.
Conclusions:
- A specific SNP in the IRF5 promoter region (rs4728142) is a significant predictor of improved survival and reduced ILD severity in systemic sclerosis patients.
- This SNP's association with lower IRF5 transcript levels suggests a potential functional mechanism influencing disease outcomes.
- These findings highlight the importance of genetic factors in determining SSc prognosis and disease manifestations.
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