MUC5B rs35705950 Promoter Variant Is Associated with Usual Interstitial Pneumonia in Patients with Antisynthetase Syndrome

<b>Background</b>: The presence of the rs35705950 variant in the <i>MUC5B</i> gene promoter is a critical genetic risk factor in idiopathic pulmonary fibrosis (IPF). It has been associated with usual interstitial pneumonia (UIP) in several interstitial lung diseases (ILDs). In antisynthetase syndrome (ASSD), most high-resolution computed tomography (HRCT) patterns are inflammatory, but up to 13% have UIP, leading to a worse prognosis. <b>Methods</b>: This single-center study included 60 patients with ASSD-ILD. We investigated whether carrying the <i>MUC5B</i> rs35705950 promoter variant was associated with UIP. To estimate the strength of the association between the genotype of the <i>MUC5B</i> rs35705950 promoter variant and the fibrotic pattern we used the odds ratio (cOR), and to assess the effect of confounding variables (age, evolution time, and sex), we performed a logistic regression to obtained the adjusted odds ratio (aOR). <b>Results</b>: The GT genotype of the <i>MUC5B</i> rs35705950 promoter variant is associated with up to a 4-fold increased risk of UIP (cOR 5.0, 95% CI 1.13-22.10), and the effect was even maintained after adjusting for potentially confounding variables such as sex, age, and time to progression (aOR 5.2, 95% CI 1.04-25.89). <b>Conclusions</b>: our study supports the role of <i>MUC5B</i> rs35705950 in ASSD-ILD with UIP. It reinforces that this polymorphism in our population could have a similar genetic basis to that already described in other ILDs that present predominantly fibrotic patterns.