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Title
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Genetic variation in interleukin-17 receptor A is functionally associated with chronic rejection after lung transplantation
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Author
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Abstract
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| 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. |
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Language
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English
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Source (journal)
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Journal of heart and lung transplantation. - St-Louis, Mo.
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Publication
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St-Louis, Mo.
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2013
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ISSN
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1053-2498
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DOI
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10.1016/J.HEALUN.2013.09.008
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Volume/pages
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32
:12
(2013)
, p. 1233-1240
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ISI
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000327688500013
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Pubmed ID
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24263024
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Full text (Publisher's DOI)
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