PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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: William S Bush; Stephen J Sawcer; Philip L de Jager; Jorge R Oksenberg; Jacob L McCauley; Margaret A Pericak-Vance; Jonathan L Haines Journal: Am J Hum Genet Date: 2010-04-01 Impact factor: 11.025
Authors: Yume Nguyen; Abed Al-Lehibi; Elizabeth Gorbe; Ellen Li; Michael Haagenson; Tao Wang; Stephen Spellman; Stephanie J Lee; Nicholas O Davidson Journal: Blood Date: 2010-02-22 Impact factor: 22.113
Authors: Sandra M P Cardoso; Todd E DeFor; Louise A Tilley; Jeffrey L Bidwell; Daniel J Weisdorf; Margaret L MacMillan Journal: Br J Haematol Date: 2004-09 Impact factor: 6.998
Authors: Steven A McCarroll; James E Bradner; Hannu Turpeinen; Liisa Volin; Paul J Martin; Shannon D Chilewski; Joseph H Antin; Stephanie J Lee; Tapani Ruutu; Barry Storer; Edus H Warren; Bo Zhang; Lue Ping Zhao; David Ginsburg; Robert J Soiffer; Jukka Partanen; John A Hansen; Jerome Ritz; Aarno Palotie; David Altshuler Journal: Nat Genet Date: 2009-12 Impact factor: 38.330
Authors: Bernd Gruhn; Juliane Intek; Nadine Pfaffendorf; Roland Zell; Selim Corbacioglu; Felix Zintl; James F Beck; Klaus-Michael Debatin; Daniel Steinbach Journal: Biol Blood Marrow Transplant Date: 2009-10-01 Impact factor: 5.742
Authors: Kim F Pearce; Stephanie J Lee; Michael Haagenson; Effie W Petersdorf; Jean Norden; Matthew P Collin; John P Klein; Stephen R Spellman; Shelagh A Lowerson; Stella Davies; Anne M Dickinson Journal: Haematologica Date: 2012-01-22 Impact factor: 9.941
Authors: Jason W Chien; Xinyi Cindy Zhang; Wenhong Fan; Hongwei Wang; Lue Ping Zhao; Paul J Martin; Barry E Storer; Michael Boeckh; Edus H Warren; John A Hansen Journal: Blood Date: 2012-01-26 Impact factor: 22.113
Authors: Francesca Bonifazi; Gianluca Storci; Giuseppe Bandini; Elena Marasco; Elisa Dan; Elena Zani; Fiorenzo Albani; Sara Bertoni; Andrea Bontadini; Sabrina De Carolis; Maria Rosaria Sapienza; Simonetta Rizzi; Maria Rosa Motta; Martina Ferioli; Paolo Garagnani; Michele Cavo; Vilma Mantovani; Massimiliano Bonafè Journal: Haematologica Date: 2013-09-20 Impact factor: 9.941
Authors: Smita Bhatia; Stella M Davies; K Scott Baker; Michael A Pulsipher; John A Hansen Journal: Biol Blood Marrow Transplant Date: 2011-07-18 Impact factor: 5.742
Authors: G Lia; L Brunello; S Bruno; A Carpanetto; P Omedè; M Festuccia; L Tosti; E Maffini; L Giaccone; M Arpinati; G Ciccone; M Boccadoro; A Evangelista; G Camussi; B Bruno Journal: Leukemia Date: 2017-08-30 Impact factor: 11.528