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Is MUC5B rs35705950 promoter polymorphism associated with chronic lung allograft dysfunction?

Year: 2025

Type: article

Abstract: Background Chronic lung allograft dysfunction (CLAD) is the main cause of death following lung transplantation (LT). Its pathophysiology and risk factors remain poorly understood. Donor or recipient genetic characteristics could be involved. MUC5B promoter rs35705950 polymorphism is one of the major genetic factors associated with pulmonary fibrosis. We aimed to correlate the MUC5B genotype of recipients and donors with LT outcomes. Methods Recipient and donor blood samples from the Cohort in Lung Transplantation biobank were used. MUC5B status was determined by quantitative PCR using probes for rs35705950 polymorphism. CLAD occurrence and phenotype were blindly adjudicated. Results 210 recipient–donor pairs were analysed. At 5 years, 68 patients (32.4%) had CLAD. The MUC5B rs35705950 polymorphism, whether in the donor or the recipient, was not associated with CLAD at 5 years (OR 1.07 (95% CI 0.53–2.11), p=0.8, and OR 0.79 (95% CI 0.37–1.60), p=0.5, respectively), CLAD-free survival or CLAD phenotype. The prevalence of the recipients’ T allele differed among underlying respiratory diseases (20.0% in interstitial lung disease, 8.4% in emphysema, 13.4% in cystic fibrosis and 5.6% for others, p=0.03). Risk of antibody-mediated rejection (AMR) was independent of the donor MUC5B polymorphism genotype, whereas the presence of the T allele in the recipient was associated with a reduced occurrence of AMR (OR 0.26 (95% CI 0.08–0.69), p=0.015). Conclusion MUC5B rs35705950 polymorphism in the donor or the recipient does not affect LT outcomes. The significant association between the recipients’ polymorphism and reduced AMR occurrence has yet to be confirmed.

Source: ERJ Open Research

DOI: 10.1183/23120541.00006-2025