Cytokine gene polymorphism and expression levels were evaluated in a group of African-American @entity1 who had undergone renal transplantation. It was hypothesized that possession of specific cytokine alleles might be influential in predisposing the recipient to allograft rejection. Thus, we sought to establish a relationship between cytokine gene polymorphism, the levels of cytokine expression, and the outcome of allograft function. Cytokine genotypes and mRNA transcript levels of @entity1199 , @entity310 , @entity2533 , @entity688 , @entity650 and @entity379 were determined using peripheral blood cells. Genomic DNA samples from 77 transplant recipients and 77 controls were tested by a multiplex PCR with specific primers for the above cytokines. The frequency distributions of cytokines were analyzed in respect to the clinical characterization, including delayed graft function (DGF), rejection episodes (REs) and stable graft function (SGF). The mRNA transcript level was tested both at pre- and early post-transplantation (day 1 and day 4) with primers for coding regions of the above cytokines in a RT-PCR assay. The majority of recipients with successful graft function were matched with their donors for only three out of the six HLA alleles. We have shown that the @entity379 T/A intermediate producer genotypes were associated with allograft rejection, whereas low @entity379 producer and high @entity688 producer genotypes were significantly protective of the allograft. There was some correlation between the @entity2533 high producer genotype and DGF, but it was not statistically significant. Overall, 77% of those who experienced REs carried the @entity2533 T/C G/G, high producer genotype as compared with 52% who experienced DGF, 39% with SGF (P<0.01, RR=2.0), and 27.3% of controls (P<0.003, RR=2.6). The @entity379 T/A intermediate producer genotype was found in 69.2% of @entity1 with REs as compared with 26.8% of @entity1 with SGF (P<0.008, RR=2.85). The @entity688 , ATA/ATA low producer genotype was found in 38.5% of recipients with REs and 14.6% of recipients without REs (P<0.04, RR=0.53). Expression levels of mRNA transcript were correlated with genotype data, except for the @entity2533 high producer genotype where there was no significant difference between the level of mRNA transcript at pre- and post-transplantation. Low DRbeta1 and high DPbeta1 expression by recipient peripheral blood mononuclear cells before transplantation was associated with more SGF, whereas high DRbeta1 and low DPbeta1 expression at pretransplantation was associated with more REs (DRbeta1, P<0.001 and DPbeta1, P<0.05, respectively). We concluded that, dual analysis of cytokine genotype and expression levels by peripheral cells may be an important clue to understanding the contribution of the recipient's immune response to an allograft pre- and post-transplantation. Identification of peripheral markers diagnostic of rejection could allow advance anticipation of clinical outcome, and might reduce the need for tissue biopsy.

Combined analysis of cytokine genotype polymorphism and the level of expression with allograft function in African-American renal transplant XXXX .

@entity1 :: ('9606', 'Species') :: ['patients'] @entity650 :: ('3569', 'Gene') :: ['IL-6'] @entity310 :: ('7124', 'Gene') :: ['TNF-alpha'] @entity2533 :: ('7040', 'Gene') :: ['TGF-beta1'] @entity379 :: ('3458', 'Gene') :: ['TGF-beta1 T/C G/G high producer and IFN-gamma', 'IFN-gamma'] @entity1199 :: ('3558', 'Gene') :: ['IL-2'] @entity688 :: ('3586', 'Gene') :: ['IL-10']
@entity1 :: (9606,Species) :: ['patients']
