MUC5B Variation and Risk for Rheumatoid Arthritis-Associated Interstitial Lung Disease

interstitial lung disease_265x125
interstitial lung disease_265x125
Researchers sought to evaluate the lifetime risk for ILD in patients with RA and estimate how the MUC5B promoter variant modifies these risks in a real-world setting.

In patients with rheumatoid arthritis (RA), MUC5B variation is strongly associated with a lifetime risk for rheumatoid arthritis-associated interstitial lung disease (RA-ILD), according to findings from a study published in the Annals of the Rheumatic Diseases.

Interstitial lung disease (ILD) is a common extra-articular complication of RA, and the MUC5B promoter variant rs35705950 is an important genetic risk factor for ILD and RA-ILD. Researchers integrated large-scale genotype data with clinical data from nationwide health care registries in Finland to estimate the lifetime risks for ILD by age 80 years with respect to the MUC5B promoter variant rs35705950. They found that out of 293,972 individuals, 0.7% developed ILD by age 80 years, with MUC5B increasing the risk for ILD with a hazard ratio (HR) of 2.44. However, out of 6869 patients diagnosed with RA, 3.6% developed ILD and MUC5B was a strong risk factor for ILD with a similar HR as the full dataset (HR: 2.27). The researchers also found that in patients with RA, lifetime risks for ILD were 16.8% for MUC5B carriers and 6.1% for MUC5B non-carriers. They noted that the difference between risks started to appear at age 65 years, and there was a higher risk in men.

“This study demonstrates the potential of genomics for risk stratification of RA-ILD and highlights the importance of genetic predisposition on the development of RA-ILD,” the study authors concluded. They added, “Studies are needed to further investigate the interaction of clinical and genetic risk factors in the development of RA-ILD, and the impact of MUC5B on outcomes of RA-ILD.”

Disclosure: This research was supported by AbbVie Inc, AstraZeneca UK Ltd, Biogen MA Inc, Celgene Corporation, Celgene International II Sàrl, Genentech Inc, Merck Sharp & Dohme Corp, Pfizer Inc, GlaxoSmithKline Intellectual Property Development Ltd, Sanofi US Services Inc, Maze Therapeutics Inc, Janssen Biotech Inc, and Novartis AG. Please see the original reference for a full list of disclosures.


Palomäki A, FinnGen Rheumatology Clinical Expert Group, Palotie A, et al. Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers. Ann Rheum Dis. Published online July 20, 2021. Doi: 10.1136/annrheumdis-2021-220698