Polymorphismen im NFKBIA Gen und akute Abstoßungsreaktionen nach Lebertransplantation

Abstract

The nuclear factor of kappa light polypeptide gene enhancer B-cells inhibitor-alpha (NFKBIA) gene encodes a member of the nuclear factor-kappa-B inhibitor family. Polymorphisms in this gene might be associated with a susceptibility to acute rejection episodes following liver transplantation, as they may cause an increased activation level of the proinflammatory transcription factor nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFκB). The aim of this study was to evaluate whether the NFKBIA polymorphisms −297 C/T (rs2233409), −826 C/T (rs2233406) and 126 G/A (rs696) affect the incidence of acute liver graft rejection. A total of 199 liver transplant recipients was analyzed, 100 without (NAR) and 99 with early acute rejection(AR). Thirty-two individuals with multiple acute rejections (MAR) were analyzed as a subgroup of AR. Polymerase chain reaction-allele specific restriction enzyme analysis (PCR-ASRA) and allele-specific hybridization with fluorescence resonance energy transfer (FRET) were used for genotyping. We identified the genotype NFKBIA 126AA (P=0.002) as well as the haplotype NFKBIA–126A–297T–826T (P=0.002) as a potential risk factor for the occurrence of recurrent acute rejections. Furthermore, we assessed an association between the 126 A allele and susceptibility to recurrent acute rejections (P=0.027). Our data suggest that the NFKBIA 126 G/A polymorphism might be potentially helpful to identify liver transplant recipients with an increased susceptibility to develop recurrent acute rejections.