Association of IL-6 promoter and IFN-γ gene polymorphisms with acute rejection of liver transplantation

Abstract

Liver transplantation is one of the most important therapies for end-stage liver diseases and is associated with major problems including infections and acute rejection. The outcome of transplantation can be determined by immune responses as a key role in response to the graft. Inflammatory and anti-inflammatory mediators especially cytokines influence the graft microenvironment. Th1 and Th2 immune responses in contrast to regulatory responses cause acute rejection or help graft survival. In this study, we evaluated the gene polymorphisms of IL-6 G-174C, TGF-β T + 869C, IL-4 C-590T, and IFN-γ T + 874A cytokines in liver transplant patients. ARMS-PCR method was used to characterize IL-6 G-174C, TGF-β T + 869C and IFN-γ T + 874A polymorphisms and PCR-RFLP using AvaII restriction enzyme was done for IL-4 C-590T characterization in 70 liver transplant patients. Acute rejection episodes were diagnosed according to standard criteria. The analysis of the results showed that IL-6-174 GG genotype ( P = 0.009, OR = 4.333, 95% CI = 1.043-18.000), IL-6-174G allele (P = 0.011, OR = 5.273, 95% CI = 1.454-19.127) was more frequent and IFN-γ +874 TT genotype was less frequent (P = 0.043, OR = 0.143, 95% CI = 0.0118-1.190) in acute rejection than in non-rejection patients. TGF-β T + 869C and IL-4 C-590T frequencies were not significantly different (P > 0.05). According to the results, it can be conclude that IL-6 G-174C and IFN-γ T + 874A gene polymorphisms have predictive values for acute rejection after liver transplantation. High producer genotype of IL-6 is a genetic risk factor and IFN-γ is a protective factor for acute rejection development.

Donor interleukin 6 gene polymorphisms predict the recurrence of hepatocellular carcinoma after liver transplantation

“…As an important component of the cytokine network, IL6 is involved in a complex series of events that control pathological and physiological changes after liver transplantation. IL6 gene polymorphisms have been shown to be predictive factors for acute rejection after liver transplantation [10,35]. In our study population of Han Chinese patients with HCC, the donor IL6 rs2069852 AA genotype was found to be a predictor for an increased risk of HCC recurrence and a decreased survival rate, suggesting that IL6 has a tumor recurrence-promoting effect after liver transplantation.…”

Association of genetic variation in co-stimulatory molecule genes with outcome of liver transplant in Iranian patients

“…Although no significant differences were observed between CTLA4 318 and CD28, significant differences between CTLA4 49 and liver transplant outcomes were detected (Marder et al, 2003b). In a previous study, we reported that there is a significant association between IFN-γ, IL-6 polymorphism liver, and kidney transplant outcome (Karimi et al, 2011(Karimi et al, , 2012.…”

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“…29,31 On the other hand, cytokines as potent immunomodulatory molecules play crucial roles in the inflammatory process, so they could determine the condition of liver microenvironment and might modulate the immune response toward rejection or acceptance of grafted liver. 32 Recent studies suggest that Th1 and Th2 cytokines may contribute to successful treatment of HBV and HCV persistent infections. 33 Little is known about the role of IL-27 in HBV pathogenesis in liver-transplanted patients, therefore, in this study the possible association of the mRNA expression level of IL-27 gene with HBV infection was evaluated.…”