The influence of glucocorticoid receptor single nucleotide polymorphisms on outcome after haematopoietic stem cell transplantation.

Autor: Norden J; Haematological Sciences, Institute of Cellular Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, UK., Pearce KF; Haematological Sciences, Institute of Cellular Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, UK., Irving JAE; Wolfson Childhood Cancer Research Centre, Northern Institute for Cancer Research, University of Newcastle upon Tyne, Newcastle upon Tyne, UK., Collin MP; Haematological Sciences, Institute of Cellular Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, UK., Wang XN; Haematological Sciences, Institute of Cellular Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, UK., Wolff D; Department of Haematology and Oncology, University of Regensburg, Regensburg, Germany., Kolb HJ; Klinikum Grosshadern, III Medical Klinik, Munich, Germany., Socie G; Department of Haematology, St Louis Hospital, Paris, France., Kuzmina Z; Department of Internal Medicine I, Bone Marrow Transplantation, Medical University of Vienna, Vienna, Austria., Greinix H; Department of Internal Medicine, Division of Haematology, Medical University of Graz, Graz, Austria., Holler E; Department of Haematology and Oncology, University of Regensburg, Regensburg, Germany., Rocha V; EUROCORD, St Louis Hospital, Paris, France., Gluckman E; EUROCORD, St Louis Hospital, Paris, France., Hromadnikova I; Department of Molecular Biology and Cell Pathology, Third faculty of Medicine, Charles University, Prague, Czech Republic., Dickinson AM; Haematological Sciences, Institute of Cellular Medicine, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
Jazyk: angličtina
Zdroj: International journal of immunogenetics [Int J Immunogenet] 2018 Jul 25. Date of Electronic Publication: 2018 Jul 25.
DOI: 10.1111/iji.12380
Abstrakt: Haematopoietic stem cell transplantation (HSCT) remains the only cure for most haematological malignancies, however, the mortality rate remains high. Complications after HSCT include relapse, graft versus host disease (GvHD), graft rejection and infection. Over the last few years several groups, have demonstrated that non-HLA gene polymorphisms can be predictive of outcome after HSCT. Since the glucocorticoid cortisol is pivotal in the regulation of the immune system, we decided to examine single nucleotide polymorphisms (SNPs; rs6198, rs33388 and rs33389) within the glucocorticoid receptor (GR) and correlate with HSCT outcome. The training set consisted of patients (n = 458) who underwent HSCT for acute leukaemia between 1983 and 2005. In the recipients, the absence of the ACT haplotype and absence of the T allele of rs33388 were associated with decreased OS and the absence of the ACT haplotype, the absence of the T allele of rs33388 and the presence of the ATA haplotype were associated with increased risk of relapse. In addition, the presence of the ACT haplotype in the recipient showed a trend to be associated with increased risk of chronic graft versus host disease (cGvHD). The patients in this cohort received mainly myeloablative conditioning (n = 327). The SNPs in the glucocorticoid receptor were then investigated in a validation set (n = 251) of HSCT patients transplanted for acute leukaemia from 2006. This cohort contained significantly more patients that had received reduced intensity conditioning (RIC). Some of the results could be validated in these patients. However, contrary to the training set, the absence of the haplotype ACT in the donor in this cohort was associated with increased risk of cGvHD. Differences in the conditioning were shown to influence the results. These results are the first to associate GR SNPs with HSCT outcome and demonstrate the inherent problems of replicating SNP association studies in HSCT, due to different pre-transplant regimens.
(© 2018 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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