Genetic variation in caveolin-1 affects survival after lung transplantation
Elly Vandermeulen1, David Ruttens, Stijn E Verleden
11 The Leuven Lung Transplant Group, Katholieke Universiteit Leuven and UZ Leuven, Leuven, Belgium. 2 Centre of Interstitial Lung Diseases, St Anthonius Hospital, Nieuwegein, The Netherlands. 3 Laboratory for Translational Genetics, Department of Oncology, KU Leuven, Leuven, Belgium. 4 Vesalius Research Center (VRC), VIB, Leuven, Belgium. 5 Centre for Environmental Sciences, Hasselt University, Diepenbeek, Belgium. 6 Department of Public Health, Katholieke Universiteit Leuven, Leuven, Belgium. 7 Address correspondence to: Bart M. Vanaudenaerde, Ph.D., K U Leuven Lung Transplantation Unit, O&N1 Herestraat 49- box 706, 3000 Leuven, Belgium.
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.
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