Genetic Variation in Caveolin-1 Affects Survival After Lung Transplantation

Abstract

Background. Caveolin-1 (CAV-1), a structural protein of the cell membrane, is involved in tissue homeostasis, inflammation, oxidative stress, microbial clearance, and fibrosis. Methods. We investigated a genetic predisposition of the CAV-1 gene on survival, acute and chronic rejection, lymphocytic bronchiolitis (LB), and respiratory infection after lung transplantation (LTx). Results. In 503 of 568 patients, the CAV-1 (rs3807989) polymorphism was successfully determined; 92 had the AA, 234 the AG, and 177 the GG genotype. Patients with the GG genotype had a decreased mortality with a adjusted hazard ratio of 0.72 (CI=0.53-0.98; P=0.034), but no association was found with chronic rejection, LB, acute rejection, or respiratory infections, although significantly less patients with the GG genotype died of infections (P=0.029). Airway neutrophilia (P=0.047) and systemic C-reactive protein (CRP, P=0.034) were decreased over time in the GG carriers compared to carriers of the A allele. Conclusion. We conclude that the GG genotype of CAV-1 is protective, associated with a decreased overall mortality but not with acute or chronic rejection, LB, and respiratory infections after LTx. The decreased mortality was linked with less infections of any kind and also lower systemic CRP, and airway neutrophils were observed, suggesting an overall decreased susceptibility for infectious complications in carriers of the GG genotype.