title: Polymorphism in NFKBIA gene is associated with recurrent acute rejections in liver transplant recipients.
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 126 AA (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.
authors.affiliation: Department of Hepatobiliary and Transplant Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, 20246, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Kramer
authors.forename: T
authors.initials: T
authors.lastname: Thye
authors.forename: A
authors.initials: A
authors.lastname: Treszl
authors.forename: S
authors.initials: S
authors.lastname: Peine
authors.forename: M
authors.initials: M
authors.lastname: Koch
authors.forename: M
authors.initials: M
authors.lastname: Sterneck
authors.forename: B
authors.initials: B
authors.lastname: Nashan
authors.forename: H
authors.initials: H
authors.lastname: Thude
mesh_terms: D000208:Acute Disease; D000328:Adult; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D060005:Genotyping Techniques; D006084:Graft Rejection / Q000235:genetics*; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
chemical_list: D020672:I-kappa B Proteins; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha
keywords: liver transplantation; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha; predictor; rejection; single nucleotide polymorphism