Association of Fc gamma-binding protein rs1464897604 polymorphism with bronchiolitis obliterans syndrome in lung transplant recipients.

Background: Bronchiolitis obliterans syndrome (BOS) is a major challenge after lung transplantation (LT) and hematopoietic stem cell transplantation (HSCT), sharing pathological similarities but lacking identified common genetic mutations.

Methods: We conducted a comparative analysis of whole-genome sequencing data from lung tissue samples of patients with BOS after LT and HSCT to identify shared and distinct genetic alterations. Common variants were validated using Sanger sequencing of peripheral blood samples. We then evaluated the association between validated variants and clinical outcomes in an independent LT cohort.

Results: Single nucleotide polymorphisms (SNPs) were the most prevalent variants in both cohorts, with a mean of 731 SNPs in post-LT BOS patients and 990 SNPs in post-HSCT BOS patients. Five candidate SNPs-FCGBP rs1464897604, KMT2C rs146238849, LINC01410 rs28440808, PABPC3 rs781717999, and POM121 rs1307236009-were selected based on their higher detection frequencies in BOS tissues compared to the general population. Sanger sequencing of blood samples confirmed that FCGBP rs1464897604 and POM121 rs1307236009 were germline variants. Among these, FCGBP rs1464897604 was prioritized for further analysis due to its relatively low minor allele frequency (MAF) in the Korean population (0.0038) and markedly higher frequency in the BOS cohort (MAF 0.4444). FCGBP rs1464897604 was significantly associated with adverse transplant outcomes, including higher rates of acute rejection, increased incidence of de novo donor-specific antibody formation within two years, and greater BOS occurrence in independent LT cohorts.

Conclusion: The common genetic variant FCGBP, identified in patients with post-HSCT and post-LT BOS, was associated with poor clinical outcomes following LT.