MUC5B promoter variant and survival in rheumatoid arthritis-associated interstitial lung disease

Objective: The objective of this study was to investigate the association between the MUC58 rs35705950 promoter variant and survival in RA-associated interstitial lung disease (RA-ILD). Methods: We studied participants in the Veteran Affairs Rheumatoid Arthritis (VARA) registry with validated ILD diagnoses. Participants were followed until death or till the end of the study period. The MUC58 rs35705950 promoter variant was measured using an Infinium genotyping array, assuming autosomal dominant inheritance. Survival and cause of death were determined from VA death records and the National Death Index. Associations of the MUC58 promoter variant with survival were tested in Cox regression models, adjusting for potential confounders. Results: Among 263 participants with RA-ILD (mean age 69 years, 95% male, 73% White, 85% smoking history), the MUC58 promoter variant was present in 33.5%. The mortality rate was similar between those with [12.2/100 PY (95% CI: 9.4, 15.8)] and without [11.1/100 PY (95% CI: 9.1, 13.5)] the variant. MUC58 status was not significantly associated with survival overall [aHR 0.97 (95% CI: 0.68, 1.37)] or when stratified by ILD pattern [clinical usual interstitial pneumonia (UIP) aHR 0.86 (95% CI: 0.55, 1.35); clinical non-UIP aHR 1.15 (95% CI: 0.63, 2.09)]. Further, MUC58 status was not significantly associated with respiratory-related [aHR 0.83 (95% CI: 0.42, 1.66)] or non-respiratory causes of death [aHR 1.08 (95% CI: 0.72, 1.62)]. Conclusion: While associated with RA-ILD risk, the MUC58 promoter variant was not predictive of survival among RA-ILD patients in this multicentre cohort. Further studies are needed to identify other genetic and non-genetic prognostic factors in RA-ILD to inform disease management.