Interleukin-6 and interferon-gamma gene polymorphisms in the development of bronchiolitis obliterans syndrome 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.
Lu
Kim C
KC
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Jaramillo
Andrés
A
Lecha
Rachel L
RL
Schuessler
Richard B
RB
Aloush
Aviva
A
Trulock
Elbert P
EP
Mendeloff
Eric N
EN
Huddleston
Charles B
CB
Alexander Patterson
G
G
Mohanakumar
T
T
D001989:Bronchiolitis Obliterans / Q000209:etiology* / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics*; D016040:Lung Transplantation / Q000009:adverse effects*; D011110:Polymorphism, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D015850:Interleukin-6; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma