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Graft-Versus-Host Disease

Oestrogen receptor α gene polymorphism associates with occurrence of graft-versus-host disease and reduced survival in HLA-matched sib-allo BMT

Bone Marrow Transplantation volume 32, pages 41–47 (2003)Cite this article

Summary:

Oestrogen receptors mediate the cellular response to oestrogens and related compounds and promote a wide range of effects on haemopoiesis. Polymorphisms of the oestrogen receptor genes have previously been associated with variation in bone mineral density, likelihood of fractures, risk of developing Alzheimer's disease, endometrial cancer and response to hormone replacement therapy. We examined the polymorphisms in both ERα and ERβ genes in 108 patients receiving a bone marrow transplant from an HLA-matched sibling donor, and compared ER genotype with outcomes of occurrence of graft-versus-host disease (GVHD) and survival using logistic regression analysis. Polymorphism of ERα (presence of the PX haplotype (PvuII–XbaI RFLP) of intron 1), but not ERβ, in the patient genotype associates with occurrence of acute GVHD and with lower overall survival, following correction for known clinical and genotypic risk features. Analysis of ER genotype prior to transplant might therefore inform on a patient's likelihood of developing post-transplant complications. Variation in transplant performance because of ER genotype suggests an underlying role for oestrogens in the pathophysiology of transplant-related complications, and suggests that oestrogen-related therapy may offer a new modality of post-transplant support.

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Acknowledgements

We thank the clinical team involved in the bone marrow transplant programme 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 & HC) and the LRF (UK) (JC and JN).

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Authors and Affiliations

  1. Department of Haematology, School of Clinical Laboratory Sciences, The Medical School, Framlington Place, Newcastle upon Tyne, UK

    P G Middleton, J Norden, H Cullup, J Cavet & A M Dickinson

  2. Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne, UK

    G H Jackson & P R A Taylor

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  1. P G Middleton
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Middleton, P., Norden, J., Cullup, H. et al. Oestrogen receptor α gene polymorphism associates with occurrence of graft-versus-host disease and reduced survival in HLA-matched sib-allo BMT. Bone Marrow Transplant 32, 41–47 (2003). https://doi.org/10.1038/sj.bmt.1704090

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