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http://hdl.handle.net/1942/16077
Title: | Genetic variation in interleukin-17 receptor A is functionally associated with chronic rejection after lung transplantation | Authors: | RUTTENS, David Wauters, Els KICINSKI, Michal Verleden, Stijn E. Vandermeulen, Elly VOS, Robin Van Raemdonck, Dirk E. NAWROT, Tim Lambrechts, Diether Verleden, Geert M. Vanaudenaerde, Bart M. |
Issue Date: | 2013 | Source: | JOURNAL OF HEART AND LUNG TRANSPLANTATION, 32 (12), p. 1233-1240 | Abstract: | BACKGROUND: Chronic rejection is the major cause of morbidity and mortality after lung transplantation. Interleukin (IL)-17-producing cells, inducers of airway neutrophilia, play a prominent role in chronic rejection. METHODS: We investigated the association between genetic variants in the lL-17/IL-23 pathway and outcome after lung transplantation. Six genetic variants in IL-17 and IL-23 receptor genes were genotyped in 497 lung transplant patients. Associations with chronic rejection, death, airway and systemic inflammatory parameters were assessed. RESULTS: The rs879574A genetic variant in the IL-17A receptor gene was associated with chronic rejection. In particular, carriers of the rs879574 at-risk A allele exhibited increased susceptibility to chronic rejection, with multivariable-adjusted hazard ratio of 1.47 (95% confidence interval, 1.07-2.03; p = 0.004), but no association was found with death (95% confidence interval, 0.71-1.41; p = 0.14). The prevalence of acute rejection was also higher in the at-risk population (p = 0.001). Interestingly, rs879574A was associated with airway neutrophilia (p = 0.020), suggesting that this variant may functionally affect the IL-17A receptor gene and thereby contribute to chronic rejection after lung transplantation. CONCLUSION: The rs879574A genetic variant is associated with chronic rejection after lung transplantation and is functionally associated with airway neutrophilia. Pre-transplant determination of this genetic variant may improve treatment and follow-up of our patients, aiming to reduce acute and chronic rejection. (C) 2013 International Society for Heart and Lung Transplantation. All rights reserved. | Notes: | Vanaudenaerde, BM (reprint author), Katholieke Univ Leuven, Lab Pneumol, Lung Transplantat Unit, Herestr 49, B-3000 Louvain, Belgium. bart.vanaudenaerde@med.kuleuven.be | Keywords: | lung transplantation; genetics; IL-17; chronic rejection; neutrophils | Document URI: | http://hdl.handle.net/1942/16077 | ISSN: | 1053-2498 | e-ISSN: | 1557-3117 | DOI: | 10.1016/j.healun.2013.09.008 | ISI #: | 000327688500013 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2014 |
Appears in Collections: | Research publications |
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