title: Defining genetic risk for graft-versus-host disease and mortality following allogeneic hematopoietic stem cell transplantation.
abstract: OBJECTIVE
  This review explores what is known about the genetics of hematopoietic stem cell transplantation (HCT) and how genetic polymorphism affects risk of graft-versus-host disease (GVHD) and mortality.
  
  
  RESULTS
  Genetic variation found across the human genome can impact HCT outcome by causing genetic disparity between patient and donor and modifying gene function. Single nucleotide polymorphism (SNP) and structural variation can result in mismatching for cellular peptides known as histocompatibility antigens. At least 25-30 polymorphic genes are known to encode functional histocompatibility antigens in mismatched individuals, but their individual contribution to clinical GVHD is unclear. HCT outcome may also be affected by polymorphism in donor or recipient. Association studies have implicated several genes associated with GVHD and mortality, however results have been inconsistent most likely due to limited sample size, and differences in racial diversity and clinical covariates. New technologies using DNA arrays genotyping for a million or more SNPs promise genome-wide discovery of HCT-associated genes, however adequate statistical power requires study populations of several thousand patient-donor pairs.
  
  
  CONCLUSIONS
  Available data offers strong preliminary support for the impact that genetic variation has on risk of GVHD and mortality following HCT. Definitive results however await future genome-wide studies of large multicenter HCT cohorts.
authors.affiliation: The Fred Hutchinson Cancer Research Center, The University of Washington School of Medicine, Seattle, Washington 98109-1024, USA. jhansen@fhcrc.org
authors.forename: John A
authors.initials: JA
authors.lastname: Hansen
authors.forename: Jason W
authors.initials: JW
authors.lastname: Chien
authors.forename: Edus H
authors.initials: EH
authors.lastname: Warren
authors.forename: Lue Ping
authors.initials: LP
authors.lastname: Zhao
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
mesh_terms: D020022:Genetic Predisposition to Disease; D006086:Graft vs Host Disease / Q000209:etiology / Q000235:genetics* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans
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