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Is MUC5B rs35705950 promoter polymorphism associated with chronic lung allograft dysfunction?
Adèle Sandot1,2, Ibrahima Ba1,3, Clément R Massonnaud4,5
1Université Paris Cité, PHERE UMRS 1152, Paris, France.
ERJ Open Research
|October 29, 2025
Summary
The MUC5B rs35705950 polymorphism in lung transplant recipients or donors does not impact chronic lung allograft dysfunction (CLAD) outcomes. However, recipient MUC5B genotype may reduce antibody-mediated rejection (AMR) risk.
Area of Science:
- Pulmonary Medicine
- Transplantation Immunology
- Genetics
Background:
- Chronic lung allograft dysfunction (CLAD) is a primary cause of mortality after lung transplantation (LT).
- The underlying pathophysiology and risk factors for CLAD are not fully understood, with potential genetic influences from donors or recipients.
- The MUC5B promoter rs35705950 polymorphism is a known genetic factor associated with pulmonary fibrosis.
Purpose of the Study:
- To investigate the association between the MUC5B rs35705950 polymorphism in lung transplant recipients and donors and their impact on LT outcomes.
- To determine if this genetic polymorphism influences the development or phenotype of CLAD.
- To explore potential correlations between MUC5B genotype and the occurrence of antibody-mediated rejection (AMR).
Main Methods:
- Analysis of recipient and donor blood samples from the Cohort in Lung Transplantation biobank.
- Determination of MUC5B rs35705950 polymorphism status using quantitative PCR.
- Blind adjudication of CLAD occurrence and phenotype in 210 recipient-donor pairs.
Main Results:
- The MUC5B rs35705950 polymorphism in either the donor or recipient was not significantly associated with CLAD at 5 years, CLAD-free survival, or CLAD phenotype.
- The prevalence of the recipient's T allele varied significantly across different underlying respiratory diseases (e.g., interstitial lung disease, emphysema, cystic fibrosis).
- While donor MUC5B genotype did not affect AMR risk, the presence of the T allele in the recipient was associated with a reduced occurrence of AMR (OR 0.26, p=0.015).
Conclusions:
- The MUC5B rs35705950 polymorphism in donors or recipients does not appear to influence overall lung transplantation outcomes related to CLAD.
- A potential protective association between the recipient's MUC5B polymorphism and a lower incidence of AMR warrants further investigation and confirmation.
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