A genetic polymorphism in the CAV1 gene associates with the development of bronchiolitis obliterans syndrome after lung transplantation

In this study, we investigated whether CAV1 genotypes associate with BOS and whether Cav-1 serum levels are influenced by the CAV1 genotype and can be used as a biomarker to predict the development of BOS.Twenty lung transplant recipients with BOS (BOSpos), ninety without BOS (BOSneg) and four hundred twenty-two healthy individuals donated DNA samples. Four SNPs in CAV1 were genotyped. Serial Cav-1 serum levels were measured in a matched cohort of 10 BOSpos patients and 10 BOSneg patients. Furthermore, single-time point Cav-1 serum levels were measured in 33 unmatched BOSneg patients and 60 healthy controls.Homozygosity of the minor allele of rs3807989 was associated with an increased risk for BOS (odds ratio: 6.13; P = 0.0013). The median Cav-1 serum level was significantly higher in the BOSpos patients than in the matched BOSneg patients (P = 0.026). Longitudinal analysis did not show changes in Cav-1 serum levels over time in both groups. The median Cav-1 serum level in the group of 43 BOSneg patients was lower than that in the healthy control group (P = 0.046).In lung transplant recipients, homozygosity of the minor allele of rs3807989 and rs3807994 was associated with increased Cav-1 serum levels.In lung transplant recipients, the CAV1 SNP rs3807989 was associated with the development of BOS and Cav-1 serum levels were influenced by the CAV1 genotype.Caveolae are 50- to 100-nm flask-shaped cell membrane invaginations in which the primary structural component is caveolin 1 (Cav-1) [1]. Cav-1 has been found in many cell types, but is abundantly expressed in endothelial cells, type 1 pneumocytes, epithelial cells, smooth muscle cells and fibroblasts [2-5]. It has many cellular functions, including vesicular transport, signal transduction and cholesterol homeostasis [1,4,6].Kasper et al. [5] were the first investigators to link Cav-1 to a fibrotic phenotype in the lungs of rats. Subsequently, studies of the role of Cav-1 in pulmonary fibrosis in humans were conduct