Blood gene expression profiling in liver transplant recipients with hepatitis C virus and posttransplantation diabetes mellitus

Background. Hepatitis C virus (HCV) is a risk factor for developing posttransplantation diabetes mellitus (PTDM) after liver transplantation; little is known about the biological mechanisms involved with this risk. This study investigated gene expression differences to provide insight into potential mechanisms. Patients and Methods. Gene expression profiles of blood samples obtained from 6 HCV+ liver transplant recipients were determined using Affymetrix U133 Plus 2.0 microarrays. Differential gene expression was assessed between HCV+ recipients with PTDM (n = 3) and without PTDM (n = 3) using the GeneSpring 7.3 software package. The Welch t test was used to identify significant differences (P < .05) between groups. Gene expression profiles for 6 HCV-liver transplant recipients (with PTDM = 3, without PTDM = 3) were used as a blind test set to evaluate a subset of genes to predict PTDM. Results. Expression levels of 347 genes were significantly different between recipients with PTDM and those without PTDM. Seventy-four genes were up-regulated and 270 were down-regulated in PTDM. Genes were categorized into functional classes: apoptosis (n = 69 genes); immune function (n = 110); diabetes (n = 17); hepatitis C (n = 12); liver transplant (n = 69). The expression profile of a subset of genes was evaluated for predicting PTDM in 6 HCV-transplant recipients. We accurately predicted the presence or absence of PTDM in 5/6 recipients. Conclusions. PTDM in HCV+ liver transplant recipients was associated with down-regulated expression of a large number of genes. A subset of these genes was useful to predict PTDM in HCV-recipients. Most genes were associated with apoptosis and immune function. HCV may act as a primer by affecting a group of genes involved in developing diabetes.