The effect of polymorphisms in tumor necrosis factor-alpha, interleukin-10, and transforming growth factor-beta1 genes in acute hepatic allograft rejection.
BACKGROUND
The occurrence of acute rejection in orthotopic liver transplantation is unpredictable. The role of cytokines in the process of rejection is not entirely clear. We investigated polymorphisms in the genes encoding tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, and transforming growth factor (TGF)-beta1, which affect the amount of cytokine produced in vitro, in a liver transplant population to determine any association with acute rejection.


METHODS
DNA was extracted from whole blood of liver transplant patients. After amplification with polymerase chain reactions, the polymorphisms at TNF-alpha -308, IL-10 -1082, and TGF-beta1 +869 and +915 were determined using sequence-specific oligonucleotide probes. Acute cellular rejection was a clinical and histological diagnosis.


RESULTS
Acute cellular rejection requiring treatment occurred in 68 (48%) of 144 patients. Acute cellular rejection was significantly associated with the TNF-alpha -308 A/A genotype (P<0.02). There was no significant association with either IL-10 or TGF-beta1 polymorphisms in acute rejection.


CONCLUSIONS
Patients with a homozygous TNF-alpha -308 genotype A/A are more likely to suffer from acute cellular rejection after liver transplantation.
Bathgate
A J
AJ
Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, United Kingdom.
Pravica
V
V
Perrey
C
C
Therapondos
G
G
Plevris
J N
JN
Hayes
P C
PC
Hutchinson
I V
IV
D000208:Acute Disease; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D016031:Liver Transplantation; D011110:Polymorphism, Genetic / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10