Gene Variant Predicts Lung Transplant Complications

Scientists have identified a genetic mutation that significantly increases the risk of life-threatening complications in lung transplant patients.

The discovery could help doctors identify high-risk patients before surgery and tailor treatment plans to improve outcomes.

Researchers at Pusan National University analyzed genetic data from lung transplant recipients and found that patients carrying a variant of the FCGBP gene faced dramatically higher rates of organ rejection, infections, and a devastating condition called bronchiolitis obliterans syndrome (BOS). The findings were published in The Journal of Heart and Lung Transplantation.

“We discovered a specific genetic variation in a gene called FCGBP that is strongly linked to bronchiolitis obliterans syndrome and poor outcomes following lung transplantation,” explains Assistant Professor Yun Hak Kim, who led the research team.

A Hidden Genetic Risk Factor

BOS affects up to half of lung transplant patients within five years of surgery. The condition causes airways to narrow and scar, leading to breathing difficulties and eventual graft failure. Until now, doctors had no way to predict which patients would develop this complication.

The research team used whole genome sequencing to analyze lung tissue samples from patients who developed BOS after both lung transplantation and stem cell transplantation. They discovered that mutations in the FCGBP gene appeared in both groups, suggesting a shared genetic pathway.

FCGBP produces a protein involved in mucus production and immune defense in the lungs. The specific variant studied—rs1464897604—appears to disrupt normal immune function, making patients more vulnerable to complications.

Striking Clinical Differences

When researchers tested the genetic variant in an independent group of 84 lung transplant patients, the results were dramatic:

• 53.8% of patients with the variant developed BOS, compared to 28.1% without it
• 44.2% experienced infections within one year, versus 18.8% in the control group
• 28.8% faced acute organ rejection, compared to 9.4% of patients with normal genes
• Overall mortality was nearly three times higher in variant carriers

From Discovery to Clinical Application

The genetic variant was particularly rare in the general Korean population, appearing in less than 0.4% of people. However, it showed up in 44% of patients who developed BOS—a thousand-fold enrichment that suggests strong biological significance.

Patients carrying the variant also showed higher rates of donor-specific antibody formation, a key mechanism in organ rejection. This finding provides insight into how the genetic mutation might disrupt normal immune tolerance of transplanted organs.

The research revealed an important detail not highlighted in the press release: patients with the FCGBP variant came from donors with significantly higher smoking histories, suggesting potential interactions between genetic susceptibility and environmental factors.

Personalized Transplant Medicine

The discovery opens new possibilities for personalized transplant care. “By testing for this genetic variation before or shortly after the transplant, doctors can adjust the treatment plan, monitor patients more closely, and take preventive steps to reduce the risk of complications like BOS,” Kim notes.

The genetic test could be incorporated into routine pre-transplant screening, allowing medical teams to:

• Intensify immunosuppressive protocols for high-risk patients
• Implement more frequent monitoring schedules
• Consider preventive treatments before complications develop
• Counsel patients about their individual risk profiles

Future research will focus on understanding exactly how the FCGBP mutation disrupts lung immunity and developing targeted therapies. The team also plans to investigate whether blood levels of the FCGBP protein could serve as a non-invasive biomarker for monitoring transplant health.

As genetic testing becomes more routine in medicine, discoveries like this demonstrate how understanding individual genetic profiles can transform patient care from reactive treatment to proactive, personalized medicine.