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

Lookup NU author(s): Dr Peter Middleton, Dr Hannah Cullup, Professor Anne Dickinson, Jean Norden, Professor Graham Jackson, Dr Penelope Taylor, Dr Jennifer Cavet


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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.

Publication metadata

Author(s): Middleton PG, Cullup H, Dickinson AM, Norden J, Jackson GH, Taylor PRA, Cavet J

Publication type: Article

Publication status: Published

Journal: Bone Marrow Transplantation

Year: 2002

Volume: 30

Issue: 4

Pages: 223-228

Print publication date: 01/08/2002

ISSN (print): 0268-3369

ISSN (electronic): 1476-5365

Publisher: Nature Publishing Group


DOI: 10.1038/sj.bmt.1703629

PubMed id: 12203138


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