Radiological Assessment in Idiopathic Pulmonary Fibrosis (IPF) Patients According to MUC5B Polymorphism
Elisabetta Cocconcelli1, Nicol Bernardinello1, Chiara Giraudo2
1Respiratory Disease Unit, Department of Cardiac Thoracic Vascular Sciences, Public Health University of Padova, 35128 Padova, Italy.
Abstract:
The MUC5B rs35705950 mutant T allele is the strongest genetic risk factor for familial and sporadic IPF. We sought to determine whether MUC5B genotype influences radiological patterns of IPF at diagnosis, as well as their change over time, in patients on antifibrotic therapy. Among eighty-eight IPF patients, previously genotyped for MUC5B rs35705950, we considered seventy-eight patients who were evaluated for radiological quantification of the following features both at treatment initiation (HRCT1) and after 1 year (HRCT2): ground glass opacities (AS), reticulations (IS) and honeycombing (HC). Of the evaluated patients, 69% carried at least one copy of the T allele (TT/TG). Carriers of the T allele displayed similar FVC loss in the first year of treatment as GG carriers, but overall survival at the end of follow-up was longer in the TT/TG group, compared to the GG group. In the GG group, both the AS and HC increased significantly, whereas in the TT/TG group only HC increased over the first year of treatment. MUC5B rs35705950 GG carriers are associated with increased ground glass and honeycombing extent over time and worse survival than T allele carriers. Longitudinal HRCT may help define the prognostic role of the MUC5B rs35705950 genotype.
Insights
Idiopathic pulmonary fibrosis (IPF) patients with the MUC5B T allele had better survival and slower disease progression than GG carriers. This MUC5B genotype influences IPF
Area of Science:
- Pulmonary Medicine
- Genetics
- Radiology
Background:
- The MUC5B rs35705950 T allele is a major genetic risk factor for idiopathic pulmonary fibrosis (IPF).
- Understanding how MUC5B genotype impacts IPF radiological patterns and progression is crucial for patient management.
Purpose of the Study:
- To investigate the influence of MUC5B rs35705950 genotype on initial radiological patterns and their changes over time in IPF patients receiving antifibrotic therapy.
- To assess the association between MUC5B genotype, radiological progression, and overall survival in IPF.
Main Methods:
- Eighty-eight IPF patients were genotyped for MUC5B rs35705950.
- Seventy-eight patients underwent high-resolution computed tomography (HRCT) at treatment initiation (HRCT1) and after 1 year (HRCT2) for quantification of ground glass opacities (AS), reticulations (IS), and honeycombing (HC).
- Longitudinal changes in radiological features and overall survival were compared between MUC5B genotype groups (TT/TG vs. GG).
Main Results:
- 69% of patients carried at least one T allele (TT/TG).
- T allele carriers (TT/TG) showed longer overall survival compared to GG carriers.
- In GG carriers, both AS and HC increased significantly over one year; in TT/TG carriers, only HC increased.
- GG carriers exhibited increased ground glass and honeycombing extent over time and worse survival than T allele carriers.
Conclusions:
- The MUC5B rs35705950 genotype significantly influences the radiological progression and survival outcomes in IPF patients on antifibrotic therapy.
- GG carriers are associated with more extensive ground glass and honeycombing progression and poorer survival.
- Longitudinal HRCT assessment, combined with MUC5B genotyping, can help elucidate the prognostic role of this genotype in IPF.
