MUC5B rs35705950 and its association with survival in Brazilian patients with idiopathic pulmonary fibrosis: A longitudinal cohort study

TL;DR

This study examines how a genetic variant in Brazilian IPF patients affects disease susceptibility and survival, finding it strongly linked to IPF risk but not to survival differences.

Contribution

Provides novel data on MUC5B rs35705950's role in IPF in a Latin American cohort, emphasizing clinical-genetic integration.

Findings

T-allele frequency was significantly higher in IPF patients compared to controls.

The MUC5B variant was strongly associated with IPF susceptibility but not with survival differences.

Higher NYHA functional class was consistently linked to increased mortality risk.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with heterogeneous clinical outcomes. The MUC5B promoter polymorphism (rs35705950) is the most consistent genetic factor associated with IPF susceptibility, but data from Latin American populations remain limited.

We conducted a longitudinal cohort study including 50 patients with IPF and 45 healthy controls, recruited between August 1, 2018, and April 30, 2025, at a tertiary referral center in Brazil. Genotyping of rs35705950 was performed by real-time PCR. Demographic, clinical, and functional data were collected at baseline. Survival was analyzed using Kaplan–Meier curves and Cox regression models, with follow-up defined from symptom onset to death or censoring.

The T-allele frequency was higher in IPF patients compared with controls (47.1% vs 8.3%, p < 0.001). Carriers of the T allele (G/T or T/T) comprised 82.4% of cases versus 16.7% of controls. Among patients with IPF, T-carriers tended to have worse lung function and shorter survival, although survival differences were not statistically significant. In multivariable models, the presence of the T allele was not an independent predictor of mortality. By contrast, higher New York Heart Association (NYHA) functional class was consistently associated with increased mortality risk.

In this Brazilian cohort, the MUC5B promoter variant was strongly associated with susceptibility to IPF but not with independent survival differences. Functional impairment, particularly NYHA class, remained the key prognostic factor. These findings highlight the importance of integrating genetic and clinical information in diverse populations and provide novel data from an underrepresented Latin American setting.

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