Please use this identifier to cite or link to this item: 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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