BACKGROUND: A number of genetic polymorphisms have been shown to regulate the production and secretion of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, interferon (IFN)-gamma, interleukin (IL)-6, and IL-10. Several of these genetic polymorphisms have been shown to be associated with either acute or chronic rejection of kidney, liver, and heart allografts and with development of allograft fibrosis after lung transplantation. The aim of this study was to assess the effect of these genetic polymorphisms on the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. METHODS: Genetic polymorphisms were detected by means of polymerase chain reaction in 93 lung allograft recipients for functional polymorphisms in the TNF-alpha (-308), TGF-beta1 (+869 and +915), IL-6 (-174), IFN-gamma (+874), and IL-10 (-1082, -819, and -592) genes. Then, a correlation between BOS development and the presence of these cytokine genotypes was determined using Kaplan-Meier actuarial analysis. RESULTS: A significant correlation was detected between the presence of high-expression polymorphisms of the IL-6 and IFN-gamma genes and BOS development after lung transplantation (P =0.045 and 0.039, respectively). Also, patients with high-expression polymorphisms in both genes developed BOS significantly earlier than patients with low-expression polymorphisms in one or both genes, suggesting a synergistic effect of the alleles during BOS pathogenesis (P =0.016). No correlation was detected between polymorphisms of the TNF-alpha, TGF-beta1, and IL-10 genes and development of BOS after lung transplantation. CONCLUSIONS: The presence of high-expression polymorphisms at position -174 of the IL-6 gene and position +874 of the IFN-gamma gene significantly increases the risk for BOS development after lung transplantation.
BACKGROUND: A number of genetic polymorphisms have been shown to regulate the production and secretion of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1, interferon (IFN)-gamma, interleukin (IL)-6, and IL-10. Several of these genetic polymorphisms have been shown to be associated with either acute or chronic rejection of kidney, liver, and heart allografts and with development of allograft fibrosis after lung transplantation. The aim of this study was to assess the effect of these genetic polymorphisms on the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. METHODS: Genetic polymorphisms were detected by means of polymerase chain reaction in 93 lung allograft recipients for functional polymorphisms in the TNF-alpha (-308), TGF-beta1 (+869 and +915), IL-6 (-174), IFN-gamma (+874), and IL-10 (-1082, -819, and -592) genes. Then, a correlation between BOS development and the presence of these cytokine genotypes was determined using Kaplan-Meier actuarial analysis. RESULTS: A significant correlation was detected between the presence of high-expression polymorphisms of the IL-6 and IFN-gamma genes and BOS development after lung transplantation (P =0.045 and 0.039, respectively). Also, patients with high-expression polymorphisms in both genes developed BOS significantly earlier than patients with low-expression polymorphisms in one or both genes, suggesting a synergistic effect of the alleles during BOS pathogenesis (P =0.016). No correlation was detected between polymorphisms of the TNF-alpha, TGF-beta1, and IL-10 genes and development of BOS after lung transplantation. CONCLUSIONS: The presence of high-expression polymorphisms at position -174 of the IL-6 gene and position +874 of the IFN-gamma gene significantly increases the risk for BOS development after lung transplantation.
Authors: Jonathan P Singer; Joshua M Diamond; Cynthia J Gries; Jamiela McDonnough; Paul D Blanc; Rupal Shah; Monica Y Dean; Beverly Hersh; Paul J Wolters; Sofya Tokman; Selim M Arcasoy; Kristy Ramphal; John R Greenland; Nancy Smith; Pricilla Heffernan; Lori Shah; Pavan Shrestha; Jeffrey A Golden; Nancy P Blumenthal; Debbie Huang; Joshua Sonett; Steven Hays; Michelle Oyster; Patricia P Katz; Hilary Robbins; Melanie Brown; Lorriana E Leard; Jasleen Kukreja; Matthew Bacchetta; Errol Bush; Frank D'Ovidio; Melanie Rushefski; Kashif Raza; Jason D Christie; David J Lederer Journal: Am J Respir Crit Care Med Date: 2015-12-01 Impact factor: 21.405
Authors: Jason W Chien; Xinyi Cindy Zhang; Wenhong Fan; Hongwei Wang; Lue Ping Zhao; Paul J Martin; Barry E Storer; Michael Boeckh; Edus H Warren; John A Hansen Journal: Blood Date: 2012-01-26 Impact factor: 22.113
Authors: Takeshi Nakajima; Vyachesav Palchevsky; David L Perkins; John A Belperio; Patricia W Finn Journal: Semin Immunopathol Date: 2011-01-27 Impact factor: 9.623
Authors: David J Hall; Maher Baz; Michael J Daniels; Edward Denmark Staples; Charles T Klodell; Lyle L Moldawer; Thomas M Beaver Journal: Interact Cardiovasc Thorac Surg Date: 2012-07-19