Association of G–137C IL-18 Promoter Polymorphism With Acute Allograft Rejection in Renal Transplant Recipients

Abstract

Interleukin 18 (IL-18) is a potent proinflammatory cytokine, which is postulated to play a role in mechanism of renal allograft rejection and strongly induces interferon (IFN)-gamma production. The aim of this study was to investigate the association of the G-137C IL-18 promoter polymorphism with acute allograft rejection in renal transplant recipients (RTRs). A total of 226 RTRs and 148 controls were recruited for association analysis. Genotyping was performed by using a real-time polymerase chain reaction. Patients were separated into two groups, the acute rejection (AR) (n=37) or the no AR group (n=189), depending on their history of AR episodes. IL-18 and IFN-gamma serum levels of 73 randomly selected RTRs were measured by ELISA. No significant differences in genotype and allele frequencies were observed between the RTRs and the controls. Significant differences in genotype frequency and allele frequency between the AR and no AR group were observed. The frequency of the -137GG genotype was significantly increased in patients with AR (P=0.015, odds ratio=3.653). Serum levels of IL-18 and IFN-gamma were significantly elevated in the AR group with compared with the no AR group. In the AR group, patients with the -137GG genotype had significantly higher IL-18 serum levels compared to other genotypes. These data demonstrate that the -137GG genotype of the IL-18 gene, encoding higher IL-18 production, seems to be associated with AR and may be a useful marker of AR risk in RTRs.