Department of Transplantation Surgery, Nagoya University, Nagoya, Japan.
J Gastrointestin Liver Dis. 2013 Jun;22(2):167-71.
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).
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.
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).
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.
尽管免疫抑制治疗有所改善,但急性细胞排斥(ACR)仍然是肝移植患者死亡和移植物丢失的重要原因。最近,已有研究报道基因多态性与 ACR 发生率之间存在关联,但很少有研究调查供体中的这些多态性。抗原加工转运体(TAP1 和 TAP2)参与主要组织相容性复合体(MHC)I 类抗原介导的加工和呈递给细胞毒性 CD8+T 淋巴细胞。本研究旨在确定供体中 TAP1 和 TAP2 基因多态性是否影响活体肝移植(LDLT)中 ACR 的发生率。
我们检查了 2004 年至 2009 年在名古屋大学和京都大学接受治疗的 155 例 LDLT,并分析了 TAP-1 p.Ile333Val、TAP-1 p.Asp697Gly、TAP-2 p.Arg651Cys 和 TAP-2 p.Gln687Stop 的基因多态性。
37 例受者发生早期 ACR。在所研究的基因多态性中,供体中的 TAP-1 p.697Gly 等位基因与早期 ACR 的发生率相关(OR=2.97,95%CI 1.33-6.63,p=0.008)。
供体中的 TAP-1 p.697Gly 等位基因与 LDLT 后早期 ACR 的发生率增加相关。供体中的 TAP-1 697 多态性可在 LDLT 前进行基因分型,这可能有助于为受者制定个体化的免疫抑制策略和供者选择。