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

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


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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.

Publication metadata

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

Publication type: Article

Publication status: Published

Journal: Bone Marrow Transplantation

Year: 2003

Volume: 32

Issue: 1

Pages: 41-47

ISSN (print): 0268-3369

ISSN (electronic): 1476-5365

Publisher: Nature Publishing Group


DOI: 10.1038/sj.bmt.1704090

PubMed id: 12815477


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