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ASSOCIATION OF TNFα AND IL10 PROMOTER POLYMORPHISMS WITH REJECTION AFTER LIVER TRANSPLANTATION IN CAUCASIAN HCV PATIENTS.
J.-Q. He , Karen Nelson , A.M. Larson , R.L. Carithers, Jr. , J.D. Perkins and L.K. Gaur . Vancouver BC, Canada, University British Columbia McDonald Research Labs ; Puget Sound Blood Center Immunogenetics ; University of Washington Laboratory Medicine ; University of Washington Surgery and Seattle WA, University of Washington, Wa Natl Primate Res Ctr .
Tumor necrosis factor α (TNFα) plays a central role in inflammation while interleukin 10 (IL10) is an important cytokine in anti-inflammatory and anti-immune functions. We hypothesized that the genetic variants of TNFα and IL10 in recipients and/or donor affect rejection reaction after liver transplantation in HCV patients. A group of 107 Caucasian liver transplant recipients with HCV infection with minimum one month follow up were studied. An average of 6.4 allograft biopsies was performed per patient. Rejection was defined by liver biopsy. One polymorphism in the TNFα gene (-308 A/G) and three polymorphisms in the IL10 gene (-1082 G/A, -819 C/T and -592 C/A) were genotyped by using PCR-SSP technique. The associations of genotype with rejection were analyzed by multiple logistic regression to adjust for potential confounding factors and to evaluate gene-gene interaction. The association between IL10 diplotype frequencies and rejection was evaluated by CLUMP software. Thirty-one out of 107 recipients (29%) developed rejection during a median of 23 months follow up period. The frequencies of genotypes of each studied TNFα and IL10 polymorphisms in recipients and donors were not different among recipients with rejection and without rejection. There were no TNFα-IL10 gene interaction in recipients or donors on rejection reaction. There were also no recipient and donor TNFα-TNFα gene interaction or recipient and donor IL10-IL10 interaction with rejection reaction. The recipient and donor TNFα and IL10 promoter polymorphisms were not associated with rejection of the graft after liver transplantation in HCV patients in our Caucasian population.