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MUC5B promoter variant rs35705950 and rheumatoid arthritis associated interstitial lung disease survival and
Pierre-Antoine Juge1, Joshua J Solomon2, Coline H M van Moorsel3
1Université de Paris, AP-HP, Hôpital Bichat Claude-Bernard, Service de Rhumatologie, DMU Locomotion, INSERM UMR1152, Paris, France.
Background:
The major risk factor for idiopathic pulmonary fibrosis (IPF), MUC5B rs35705950, was found to be associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Whilst the MUC5B rs35705950 T risk allele has been associated with better survival in IPF, its impact on RA-ILD prognosis remains to be determined. Our objective was to explore the influence of MUC5B rs35705950 on survival and progression in RA-ILD.
Methods:
Through an international retrospective observational study, patients with RA-ILD were genotyped for the MUC5B rs35705950 variant and consecutive pulmonary function tests (PFTs) findings were collected. Longitudinal data up to a 10-year follow-up were considered and analyzed using mixed regression models. Proportional hazards and joint proportional hazards models were used to analyze the association of baseline and longitudinal variables with lung transplant-free survival. Significant progression of RA-ILD was defined as at least an absolute or relative 10% decline of forced vital capacity at 2 years from baseline.
Results:
Out of 321 registered patients, 261 were included in the study: 139 women (53.3%), median age at RA-ILD diagnosis 65 years (interquartile range [IQR] 57 to 71), 151 ever smokers (59.2%). Median follow-up was 3.5 years (IQR 1.3 to 6.6). Mortality rate was 32% (95%CI 19 to 42) at 10 years. The MUC5B rs35705950 variant did not impact lung transplant-free survival (HR for the T risk allele carriers=1.26; 95%CI 0.61 to 2.62; P=0.53). Decline in pulmonary function at 2 years was not influenced by MUC5B rs35705950 (OR=0.95; 95%CI 0.44 to 2.05; P=0.89), irrespective of the HRCT pattern.
Conclusion:
In this study, the MUC5B rs35705950 promoter variant did not influence transplant- free survival or decline in pulmonary function in patients with RA-ILD.
Insights
The MUC5B rs35705950 variant, a risk factor for idiopathic pulmonary fibrosis, did not affect survival or lung function decline in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). This finding differs from its known impact on IPF prognosis.
Area of Science:
- Pulmonology
- Genetics
- Rheumatology
Background:
- The MUC5B rs35705950 variant is a major risk factor for idiopathic pulmonary fibrosis (IPF).
- This variant has been linked to rheumatoid arthritis-associated interstitial lung disease (RA-ILD).
- The T risk allele of MUC5B rs35705950 is associated with better survival in IPF, but its effect on RA-ILD prognosis is unknown.
Purpose of the Study:
- To investigate the influence of the MUC5B rs35705950 variant on survival and disease progression in patients with RA-ILD.
Main Methods:
- An international retrospective observational study involving genotyping of MUC5B rs35705950 in RA-ILD patients.
- Collection of consecutive pulmonary function test (PFT) data over a 10-year follow-up period.
- Analysis using mixed regression models, proportional hazards, and joint proportional hazards models to assess survival and progression.
Main Results:
- The MUC5B rs35705950 variant did not significantly impact lung transplant-free survival in RA-ILD patients.
- Decline in pulmonary function over 2 years was not influenced by the MUC5B rs35705950 variant.
- These findings were consistent regardless of the high-resolution computed tomography (HRCT) pattern.
Conclusions:
- The MUC5B rs35705950 promoter variant does not appear to influence transplant-free survival or pulmonary function decline in RA-ILD.
- This suggests a differential impact of the MUC5B rs35705950 variant on RA-ILD compared to IPF.
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