Role of cytokine gene polymorphism in hepatitis C recurrence and allograft rejection among liver transplant recipients

Cytokines play a key role in the regulation of immune responses. The maximal capacity of cytokine production varies between individuals and was shown to correlate with polymorphism in cytokine gene promoters. The objective of this study was to analyze the role of cytokine allelic variations in susceptibility to early graft rejection episodes and recurrence of hepatitis C infection in liver transplant (LTx) recipients. The genetic profile of five cytokines was studied in 68 LTx recipients and 49 controls using polymerase chain reaction sequence specific primers. All individuals were genotyped as high or low producers of TNF-alpha and IL-6 and high, intermediate, or low producers of transforming growth factor beta (TGF-beta), interferon gamma (IFN-gamma), and interleukin 10 (IL-10) based on single nucleotide substitutions. No statistically significant differences were observed between patients with or without early rejection episodes. A significant proportion of patients more prone to rejection were genotyped as having a low production profile of IL-10 compared with the control population (P=0.04). These data are in accordance with reports regarding other solid-organ transplant recipients. Patients with no recurrence of hepatitis C had the inherent ability to produce higher TGF-beta levels than did patients with recurrent disease (P=0.042). Among nonrecurrent patients, the percentage of genetically low IL-10 producers was higher than among recurrent patients (P=0.07). Furthermore, a genetic tendency to produce higher levels of IFN-gamma was noted among LTx recipients with nonrecurrent hepatitis C than among those with recurrent hepatitis C. While no significant correlation was detected between particular cytokine profile and early rejection episodes, our data strongly suggest an association between cytokine gene polymorphism of TGF-beta, IL-10, and INF-gamma and recurrence of hepatitis C in LTx recipients.