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Allografting

Genetic polymorphisms in the genes encoding human interleukin-7 receptor-α: prognostic significance in allogeneic stem cell transplantation

Bone Marrow Transplantation volume 37, pages 485–491 (2006)Cite this article

Abstract

Interleukin-7 (IL-7) is essential for T-cell development in the thymus and for the maintenance of peripheral T cells. IL-7 signals through IL-7R, that consists of the γc-chain and an α-chain. Sequencing of IL-7Rα has revealed the existence of four single nucleotide polymorphisms (SNPs) (+510C/T, +1237 A/G, 2087T/C and +3110A/G), which all give rise to amino-acid substitutions. The aim of the present investigation was to evaluate the significance of IL-7Rα SNPs for the outcome in allogeneic stem cell transplantation (SCT). IL-7Rα polymorphisms were determined in 195 recipient and donor pairs from either matched sibling donors or matched unrelated donors (MUD). Genotyping of 173 normal controls was performed in parallel. In MUD transplants, the +1237 genotype of the donor was associated with survival after SCT, the mortality being highest and intermediate for the GG and AG genotypes, respectively (P=0.023). This pattern was more pronounced with respect to treatment-related mortality (P=0.003), while IL-7Rα genotypes were unrelated to the risk of relapse of leukaemia. The IL-7Rα +1237 genotype of the recipient and the genotypes of the other three polymorphisms, were not significantly associated with the outcome of SCT. These findings suggest that the IL-7Rα polymorphisms may be of importance for treatment-related mortality after SCT.

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Acknowledgements

Financial support was obtained from The Danish Research Council, The Danish Cancer Association, The Lundbeck Foundation, The Dagmar Marshall Foundation, The Lilly Benthine Lunds Foundation, The Research Council at Rigshospitalet and The Carla Thiel Kragh Foundation.

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Author notes

  1. Z Shamim and L P Ryder: Shared first-authorship.

Authors and Affiliations

  1. The Tissue Typing Laboratory, Rigshospitalet, Copenhagen, Denmark

    Z Shamim, L P Ryder, H Madsen & A Svejgaard

  2. Department of Paediatrics, Rigshospitalet, Copenhagen, Denmark

    C Heilmann & K Müller

  3. Department of Haematology, Rigshospitalet, Copenhagen, Denmark

    H Lauersen & N Jacobsen

  4. Department of Biostatistics, University of Copenhagen, Denmark

    P K Andersen

  5. The Institute of Inflammation Research, Rigshospitalet, Copenhagen, Denmark

    K Müller

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  1. Z Shamim
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  2. L P Ryder
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  3. C Heilmann
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  5. H Lauersen
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  6. P K Andersen
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  7. A Svejgaard
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Correspondence to K Müller.

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Shamim, Z., Ryder, L., Heilmann, C. et al. Genetic polymorphisms in the genes encoding human interleukin-7 receptor-α: prognostic significance in allogeneic stem cell transplantation. Bone Marrow Transplant 37, 485–491 (2006). https://doi.org/10.1038/sj.bmt.1705277

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  • DOI: https://doi.org/10.1038/sj.bmt.1705277

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