Investigation of promoter polymorphisms in the tumor necrosis factor-alpha and interleukin-10 genes in liver transplant patients.
BACKGROUND
Cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 play significant roles in the inflammatory and immune responses that mediate allograft rejection. The presence of a G-->A polymorphism at position -308 in the promoter region of the TNF-alpha gene increased its transcription 6- to 7-fold. A similar polymorphism at position -1082 of the IL-10 promoter results in decreased production of IL-10 protein. In this study we have determined whether the single nucleotide polymorphisms in the promoter regions of the TNF-alpha and IL-10 genes can predict the outcome of the allograft in liver recipients.


METHODS
DNA was extracted from whole blood of liver recipients. The genotype of the patients was determined by polymerase chain reaction using sequence-specific primers. The level of TNF-alpha and IL-10 protein was measured by ELISA after stimulation of peripheral blood mononuclear cells with concanavalin A.


RESULTS
There was significant correlation between acute cellular rejection and the presence of the -308A polymorphism (P<0.001), with 8 of 13 patients with the TNF-alpha polymorphism having evidence of acute rejection. Cell stimulation studies revealed that the level of TNF-alpha protein produced by patients with liver rejection was significantly higher than for patients without rejection (P=0.001). There were no strong associations between the presence of the IL-10 polymorphisms and rejection (P=0.71).


CONCLUSIONS
This study adds to the understanding of the role of cytokine polymorphisms in liver transplants. The data suggest that cytokine promoter polymorphisms may be a risk factor associated with allograft rejection in the liver.
Fernandes
Helen
H
Department of Pathology and Laboratory Medicine, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA. fernande@umdnj.edu
Koneru
Baburao
B
Fernandes
Neil
N
Hameed
Meera
M
Cohen
Marion C
MC
Raveche
Elizabeth
E
Cohen
Stanley
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005838:Genotype; D006084:Graft Rejection; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D016031:Liver Transplantation; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10