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TheMUC5Bgene codes for mucin - a protein that is normally found in mucus secretions, and which is part of the body's natural defense against infection. The promoter variantcalledrs35705950is a common variant in the MUC5B gene, with an allele frequency of 0.1 in the Finnish population. Overexpression ofMUC5Bin lungs influences the development of pulmonary fibrosis. The promoter variant rs35705950 in MUC5B is the strongest known genetic risk factor for rheumatoid arthritis-associated interstitial lung disease (RA-ILD). However, there are no large-scale data on the impact oftheMUC5Bpromoter variant on the long-term incidence of RA-ILD.
AnttiPalomäkiand colleagues used FinnGen- a collection of epidemiological cohorts and hospital biobank samples - to describe the long-term risk of RA-ILD in people with RA carrying the MUC5B promoter variant compared to those without the variant. FinnGen is able to link people's genetic information with up to 46 years of follow-up data within nationwide registries.
Of 248,400people, 5534 had been diagnosed with RA, and 178 of these (3.2%) had developed ILD.TheMUC5Bpromoterwas a strong predictor ofdevelopingILD in people with RA, conferring a lifetime risk of ILD of 14.5%by age 80, compared to 5.2% in people with RA who did not carry the promoter variant. In the general population of people without RA, MUC5B promoter carriers and non-carriers had lifetime risks of developing ILD of3.9% and 1.3%, respectively.
The authors found that the risk difference started to emerge attheageof65. The risk was highest in men with RA who areMUC5Bcarriers. In this group, 18.5%of carriers developed ILD, compared to 8.5% of non-carriers.
These findings have clinical implications for improving identification of people with RA who are at high risk for developing ILD.