Article Text

Download PDFPDF

  1. A. Palomäki1,
  2. T. Laitinen2,
  3. J. Koskela3,
  4. A. Palotie3,4,5,
  5. N. Mars3
  6. on behalf of FinnGen
  1. 1Turku University Hospital, Centre for Rheumatology and Clinical Immunology, Turku, Finland
  2. 2Tampere University Hospital, Administration Center, Tampere, Finland
  3. 3University of Helsinki, Institute for Molecular Medicine Finland, FIMM, HiLIFE, Helsinki, Finland
  4. 4Massachusetts General Hospital, Analytic and Translational Genetics Unit, Department of Medicine, Boston, United States of America
  5. 5Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, United States of America


Background: The promoter variant rs35705950 in MUC5B is the strongest known genetic risk factor for rheumatoid arthritis-associated interstitial lung disease (RA-ILD) [1]. 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: [1]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

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.