Cytokine gene polymorphisms are not associated with bronchiolitis obliterans syndrome or survival after lung transplant.
BACKGROUND
Cytokine polymorphisms are inconsistently associated with transplant rejection and other adverse outcomes. To address this controversy, we evaluated cytokine single nucleotide polymorphisms (SNPs) in a lung transplant cohort.


METHODS
All patients who underwent lung transplantation from 1993 to 1998 and had post-transplant survival of at least 6 months were included in the initial analysis. Subjects were genotyped for: TNF-alpha -308 G/A; IFN-gamma +874 A/T; TGF-beta1 +869 T/C and +915 G/C; IL-10 -1082 A/G, -819 C/T and -592 C/A; and IL-6 -174 G/C. End-points were onset of broncholitis obliterans syndrome (BOS) and survival.


RESULTS
In the cohort, 78 subjects, with an overall mean +/- SE survival 2,339 +/- 117 days, had no correlation between onset of BOS1, BOS2 or survival with TNF-alpha, IFN-gamma, TGF-beta1 or IL-10 gene polymorphisms. However, IL-6 polymorphisms GG or GC were associated with an earlier onset of BOS1 (p = 0.039), BOS2 (p = 0.021), and decreased overall post-transplant survival (p = 0.038). A second cohort of more recent lung transplant recipients did not validate an association between IL-6 polymorphisms and earlier onset of BOS1 (p = 0.70), BOS2 (p = 0.54) or overall post-transplant survival (p = 0.25).


CONCLUSIONS
Polymorphisms of TNF-alpha, IFN-gamma, TGF-beta1, IL-10 and IL-6 do not appear to influence the onset of BOS or graft survival in recipients.
Snyder
Laurie D
LD
Division of Pulmonary, Allergy and Critical Care, Duke University Medical Center, Durham, North Carolina 27710, USA. snyde014@mc.duke.edu <snyde014@mc.duke.edu>
Hartwig
Matthew G
MG
Ganous
Tonya
T
Davis
R Duane
RD
Herczyk
Walter F
WF
Reinsmoen
Nancy L
NL
Schwartz
David A
DA
Palmer
Scott M
SM
D000293:Adolescent; D000328:Adult; D000368:Aged; D001989:Bronchiolitis Obliterans / Q000235:genetics* / Q000401:mortality* / Q000601:surgery; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006085:Graft Survival / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016040:Lung Transplantation / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015996:Survival Rate; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D015850:Interleukin-6; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma