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Immunobiology

Vitamin D receptor gene polymorphism associates with graft-versus-host disease and survival in HLA-matched sibling allogeneic bone marrow transplantation

Bone Marrow Transplantation volume 30, pages 223–228 (2002)Cite this article

Abstract

We investigated the role of polymorphism of the vitamin D receptor (VDR) gene in HLA-matched sibling BMT for polymorphisms previously associated with human disease pathology. In intron 8 of the VDR gene, the B and A alleles of the BsmI and ApaI RFLPs were found to associate with reduced aGVHD when present in the patient's genotype. Logistic regression analysis demonstrated that patient VDR genotype, along with previously identified IL-10−1064 and IFN-γ genotype to be risk factors for severe acute GVHD. The A allele also associates with increased likelihood of death when present in the donor genotype (AA vs Aa or aa, hazard ratio 2.03, P = 0.0232). In patients who received increased prophylaxis with multi-agent therapy, patients whose graft was from a donor with an AA genotype had a substantially worse survival than patients whose graft was from a donor with a non-AA genotype (hazard ratio 12.93, P < 0.0001). Analysis of VDR genotype in prospective BMT recipients could indicate patients at risk of severe aGVHD. Analysis of VDR genotype in prospective BMT donors may identify individuals who have greater transplant-related mortality, and also allow appropriately restricted use of increased immunosuppressive prophylaxis.

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Acknowledgements

Many thanks to the clinical team involved in the bone marrow transplant program at the Royal Victoria Infirmary, Newcastle upon Tyne, particularly Professor SJ Proctor, Dr A Lennard and Dr PJ Hamilton. This work was supported by the Tyneside Leukaemia Research Association (AMD), and the Leukaemia Research Fund, UK (JC).

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  1. University Department of Haematology, The Medical School, Newcastle upon Tyne, UK

    PG Middleton, H Cullup, AM Dickinson, J Norden, GH Jackson, PRA Taylor & J Cavet

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  1. PG Middleton
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Middleton, P., Cullup, H., Dickinson, A. et al. Vitamin D receptor gene polymorphism associates with graft-versus-host disease and survival in HLA-matched sibling allogeneic bone marrow transplantation. Bone Marrow Transplant 30, 223–228 (2002). https://doi.org/10.1038/sj.bmt.1703629

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