ROLE OF CYTOKINE GENE POLYMORPHISM IN HEPATITIS C RECURRENCE AND ALLOGRAFT REJECTION AMONG LIVER TRANSPLANT RECIPIENTS 1

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Abstract
Cytokines play a key role in the regulation of immuneresponses. The maximal capacity of cytokine production varies betweenindividuals and was shown to correlate with polymorphism in cytokine genepromoters. The objective of this study was to analyze the role of cytokineallelic variations in susceptibility to early graft rejection episodes andrecurrence of hepatitis C infection in liver transplant (LTx)recipients. The genetic profile of five cytokines was studied in 68 LTxrecipients and 49 controls using polymerase chain reaction sequence specificprimers. All individuals were genotyped as high or low producers of TNF-αand IL-6 and high, intermediate, or low producers of transforming growthfactor β (TGF-β), interferon γ (IFN-γ), and interleukin 10(IL-10) based on single nucleotidesubstitutions. No statistically significant differences were observedbetween patients with or without early rejection episodes. A significantproportion of patients more prone to rejection were genotyped as having a lowproduction profile of IL-10 compared with the control population(P =0.04). These data are inaccordance with reports regarding other solid-organ transplant recipients.Patients with no recurrence of hepatitis C had the inherent ability to producehigher TGF-β levels than did patients with recurrent disease(P =0.042). Among nonrecurrentpatients, the percentage of genetically low IL-10 producers was higher thanamong recurrent patients(P =0.07). Furthermore, agenetic tendency to produce higher levels of IFN-γ was noted among LTxrecipients with nonrecurrent hepatitis C than among those with recurrenthepatitis C. While no significant correlation was detected betweenparticular cytokine profile and early rejection episodes, our data stronglysuggest an association between cytokine gene polymorphism of TGF-β, IL-10,and INF-γ and recurrence of hepatitis C in LTxrecipients.