Association of transporter associated with antigen processing (TAP) gene polymorphisms in donors with acute cellular rejection in living donor liver transplantation

Background & Aims: Despite improvements in immunosuppressive therapy, acute cellular rejection (ACR) remains an important cause of mortality and graft loss in patients undergoing liver transplantation. Recently, associations between gene polymorphisms and the incidence of ACR have been reported, though few studies have investigated those polymorphisms in donors. Transporter associated with antigen processing (TAP1 and TAP2) are involved in major histocompatibility complex (MHC) class I antigen-mediated processing and presentation to cytotoxic CD8+ T lymphocytes. The aim of this study was to determine whether TAP1 and TAP2 gene polymorphisms in the donor have affected on ACR incidence in living donor liver transplantation (LDLT). Methods: We examined 155 LDLTs treated at Nagoya University or Kyoto University from 2004 to 2009 and analyzed the gene polymorphisms of TAP-1 p.Ile333Val, TAP-1 p.Asp697Gly, TAP-2 p.Arg651Cys, and TAP-2 p.Gln687Stop. Results: Thirty-seven recipients developed early ACR. Of the investigated gene polymorphisms, the TAP-1 p.697Gly allele in donors was associated with incidence of early ACR (OR=2.97, 95%CI 1.33-6.63, p=0.008). Conclusions: The TAP-1 p.697Gly allele in donors was associated with increased incidence of early ACR following LDLT. The TAP-1 697 polymorphism in donors can be genotyped prior to LDLT, which may contribute to individualize immunosuppression strategies for recipients and donor selection.