Background: The promoter variant rs35705950 in MUC5B is the strongest known genetic risk factor for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) . There is, however, no large-scale data on the impact of MUC5B on the long-term incidence of RA-ILD.
Objectives: To describe long term risk of RA-ILD in RA patients carrying MUC5B variant compared to non-carriers with RA.
Methods: FinnGen is a collection of epidemiological cohorts and hospital biobank samples, linking genotypes with up to 46 years of follow-up within nationwide registries. Diagnoses of RA and ILD were identified from the Finnish national hospital discharge, medication reimbursement and cause-of-death registries. We estimated lifetime risks of ILD by age 80. MUC5B is a common variant and has an allele frequency of 0.1 in the Finnish population.
Results: Out of the 248,400 individuals, 5534 patients have been diagnosed with RA, out of whom 178 (3.2%) developed ILD. MUC5B was a strong predictor of ILD in RA patients (HR 2.14, 95%CI 1.56-2.92). In patients with RA, MUC5B conferred a lifetime risk of 14.5% (95%CI 10.7-18.1%), compared to 5.2% (4.1-6.2%) in MUC5B non-carriers with RA (Figure). In the population, MUC5B carriers and MUC5B non-carriers had lifetime risks of 3.9% and 1.3%, respectively. The risk difference started to emerge at age 65. The risk was highest in men with RA who are MUC5B carriers: 18.5% (11.1-25.2%) developed ILD, compared to 8.5% (6.1-10.9%) of MUC5B non-carriers with RA.
Conclusion: We report findings from a large longitudinal study, showing that MUC5B confers a considerable lifetime risk of RA-ILD, and contributes to increased morbidity. These findings have clinical implications for improving identification of RA patients at high risk of developing ILD.
References: Juge P-A, Lee JS, Ebstein E, et al. MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease. N Engl J Med 2018;379:2209–19
Disclosure of Interests: Antti Palomäki Speakers bureau: MSD, Pfizer, Sanofi, Consultant of: Pfizer, Abbvie, Tarja Laitinen: None declared, Jukka Koskela Speakers bureau: Pfizer, Aarno Palotie: None declared, Nina Mars: None declared
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