Norden, Jean and Pearce, Kim F. and Irving, Julie A. E. and Collin, Matthew P. and Wang, Xiao N. and Wolff, Daniel and Kolb, Hans-Jochem and Socie, Gerard and Kuzmina, Zoya and Greinix, Hildegard and Holler, Ernst and Rocha, Vanderson and Gluckman, Eliane and Hromadnikova, Ilona and Dickinson, Anne M. (2018) The influence of glucocorticoid receptor single nucleotide polymorphisms on outcome after haematopoietic stem cell transplantation. INTERNATIONAL JOURNAL OF IMMUNOGENETICS, 45 (5). pp. 247-256. ISSN 1744-3121, 1744-313X
Full text not available from this repository. (Request a copy)Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VERSUS-HOST-DISEASE; RHEUMATOID-ARTHRITIS; GENE POLYMORPHISMS; RISK; MARROW; SUSCEPTIBILITY; SURVIVAL; DONORS; chronic graft versus host disease; haplotype; inflammation aGVHD; polymorphisms; relapse |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Dec 2019 09:51 |
| Last Modified: | 12 Dec 2019 09:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/13819 |
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