Association of HLA-G 14 bp Deletion/Insertion Polymorphism with Kidney Allograft Outcome in Northwestern Chinese Han Population

Abstract

Introduction: During the 1990s, human leukocyte antigen (HLA)-G was shown to play a role in maternal-fetal tolerance, to date, the expression of HLA-G was studied in organ transplantation, and the results obtained show that patients expressing HLA-G in the graft exhibit significantly better graft acceptance. HLA-G also play an important role in promote transplantation tolerance. Then, whether HLA-G 14 bp deletion/insertion polymorphism association with kidney allograft outcome and may be a valuable marker for the prediction of allograft rejection. Although the HLA polymorphism has been extensively studied, the present work is the first to show data related to14 bp insertion/deletion polymorphism in a group of normal and kidney transplant recipients in northwestern Chinese Han population. Methods: The study was approved by the local ethical committee. Peripheral blood samples of 2 ml anticoagulated whole blood were obtained from 95 renal transplant recipients underwent kidney transplantation with living-related donor. In addition, we obtained whole blood from 89 healthy volunteers (HV) as controls. Posttransplant patients were divided into tow groups depending on their clinical course: 43 patients have had acute rejection (AR), and 52 patients were nonrejection group (NRG). Genomic DNAs were extracted from 250 μl of cell suspension by the E.Z.N.A. ® Blood DNA Kit. HLA-G 14 bp insertion/deletion polymorphism (rs16375) was amplified by polymerase chain reaction. Results: In this study, no significant difference was found among AR, NRG and the HV regarding the age, gender, panel reaction antibody (PRA), mismatches HLA, cold ischemic time and immunosuppressive treatment. The genotype and allele frequencies in different groups were shown in Table 1. No departures from Hardy-Weinberg equilibrium were found. Frequency of the genotypes +14/+14 bp, +14/-14 bp and -14/-14 bp in HV were 13.5%, 51.7% and 34.8%, respectively, in AR were 39.5%, 41.9% and 18.6%, and in NRG were 19.2%, 48.1% and 32.7%. There was an increased genotype (+14/+14 bp) in the group of AR compare with NRG. At the same time, frequency of the allele +14 in the group of AR significantly higher than NRG.[Table 1 Distribution of HLA-G 14-bp polymorphism.]Conclusion: This study showed in northwestern Chinese Han population, the homozygous genotype +14/+14 bp and the allele +14 were significantly increased in the group with acute rejection, which indicate that the 14-bp insertion/deletion polymorphism might be important for the outcome of a kidney transplantation. HLA-G 14 bp deletion/insertion polymorphism may be an important prognostic tool to guide post-transplant immunosuppressive therapy.