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Association analysis between SUFU polymorphism rs17114808 and acute graft versus host disease after hematopoietic stem cell transplantation

Bone Marrow Transplantation volume 53, pages 377–382 (2018)Cite this article

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For many hematological malignancies, allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative option. However, only 30–75% of patients find a fully matched human leukocyte antigen (HLA) donor [1]. Hence, HLA-mismatched donors are used for HSCT although HLA mismatch is associated with increased incidence of graft versus host disease (GvHD) and inferior overall survival [1]. GvHD is a severe, life-threating complication, which is even lethal for approximately 15% of patients [2]. Besides the effect of HLA disparity, disease stage, type of conditioning prior to HSCT, age, immunosuppression, donor, and recipient sex, type of prophylaxis, prior exposure to viruses, and use of stem cells from peripheral blood influence the incidence of GvHD [3, 4]. Furthermore, different genetic polymorphisms affect the risk for GvHD, especially genes encoding for cytokines or chemokines, pharmacogenes and costimulatory molecules [5]. For example, Kim et al. discovered an association between the presence of a specific single-nucleotide polymorphisms (SNP) in the NFKBIA or in the FAS gene of the recipient with increased risk of acute GvHD and the group suggested a SNP-based approach to improve the risk stratification of GvHD [6, 7]. In addition, various SNPs in donors’ or recipients’ genes were associated with an effect on the risk and/or the outcome of GvHD after HSCT, e.g., ABCB1, CYP3A, thrombomodulin, Interleukin-17, methylenetetrahydrofolate reductase, B-cell activating factor, Interleukin-2, tumor necrosis factor-α, and heparanase [8,9,10,11,12,13,14].

Recently, Bari et al. showed a correlation of the suppressor of fused (SUFU) polymorphism rs17114808 (C/T, 3′ untranslated region) and the incidence of acute GvHD [15]. In total, they analyzed n = 168 pediatric patients after allogeneic hematopoietic stem cell transplantation (HSCT), divided into a discovery cohort of n = 68 patients and a validation cohort of n = 100 patients. The authors found a higher incidence of acute GvHD in both cohorts when patients were homozygous for CC, whereas heterozygous (CT) individuals developed less GvHD. Their genetic findings were supported by functional studies, which revealed lower expression of SUFU protein in dendritic cells of CC healthy donors that in turn increased HLA-DR expression and T-cell proliferation.

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Acknowledgements

This work was supported by the Stiftung für krebskranke Kinder Tübingen e.V, the Stefan-Morsch-Stiftung, and the José Carreras Leukämie-Stiftung.

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  1. Department of General Paediatrics, Haematology/Oncology, University Children’s Hospital, 72076, Tübingen, Germany

    Marie C. Katz, Sebastian Michaelis, Darina M. Siegmund, Renate Koch, Rupert Handgretinger & Markus Mezger

  2. Medical Center, Department of Hematology and Oncology, University of Tuebingen, 72076, Tübingen, Germany

    Wolfgang Bethge

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Katz, M.C., Michaelis, S., Siegmund, D.M. et al. Association analysis between SUFU polymorphism rs17114808 and acute graft versus host disease after hematopoietic stem cell transplantation. Bone Marrow Transplant 53, 377–382 (2018). https://doi.org/10.1038/s41409-017-0059-3

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