Polymorphisms in cytokines and growth factor genes and their association with acute rejection and recurrence of hepatitis C virus disease in liver transplantation

Acute rejection (AR) and recurrence of hepatitis C virus (HCV) infection are complications after liver transplantation (LTx). Genetic factors play a role in cytokine production as a consequence of polymorphisms within cytokine genes. Our goal was to identify genetic factors that might be associated with AR and recurrence of HCV in liver transplant recipients (LTxRs). We studied 77 Caucasian LTxRs and 100 Caucasian healthy individuals. We studied single-nucleotide polymorphisms (SNPs) in tumor necrosis factor-alpha [TNF-alpha, interleukin-6 (IL-6), IL-10, transforming growth factor-beta1, and angiotensin-converting enzyme genes by SNaPSHOT(TM) Multiplex assay. SNPs were classified as high producers (HP), intermediate producers (IP), or low producers (LP),. and their association with AR and recurrence of HCV were studied. The frequency of TNF-alpha IP and HP genotypes was significantly higher in LTxRs with AR in comparison to patients without AR (TNF-alpha HP -238: 63 vs 20%, p < 0.001; TNF-alpha HP -308: 47.4 vs 20%, p = 0.02). The frequency of IL-6 IP and HP genotypes was higher in patients with AR episodes, but the difference was not statistically significant (p = 0.14). However, when we analyzed the simultaneous presence of pro-inflammatory genotypes in the same patient. we found a significant difference between patients with and without AR. respectively (42.1 vs 14.6%, p = 0.012). Moreover, the frequency of the IL-10 LP genotype was higher in LTx patients with AR (p = 0.001) compared to patients without AR. There was an association between pro-inflammatory genotypes and HCV recurrence. Our data suggest that cytokine gene polymorphisms might play a role in AR and HCV recurrence in LTxRs.