Influence of polymorphism within the heme oxygenase-I promoter on overall survival and transplantation-related mortality after allogeneic stem cell transplantation.
Aside from major and minor histocompatibility antigens, genetic polymorphisms of various donor and host genes have been found to be risk factors for graft-versus-host disease and transplantation-related mortality (TRM). The heme oxygenase I (HO-I) protein has been implicated in regulating inflammatory response and has been described as a "protective gene" in solid organ transplantation. In humans, the promoter region displays length polymorphism due to a variable number of GT repeats. Individuals exhibiting 29 or fewer GT repeats express higher levels of HO-I on cellular stress compared with individuals with 30 or more GT repeats. We retrospectively analyzed length polymorphisms of 92 donor-host pairs undergoing allogeneic stem cell transplantation. Our findings demonstrate that mainly donor polymorphism leading to high expression of HO-1 (<30 GT repeats) on stress signals is associated with reduced overall survival, and that TRM is significantly increased in this group. This reduction in survival was most prominent when unrelated donors were used. Polymorphisms of the recipient HO-1 genes did not influence posttransplantation outcomes. We conclude that HO-1 polymorphism represents a new genetic risk factor for TRM and overall survival.
Gerbitz
Armin
A
Department of Hematology and Oncology, Charité Berlin, Campus Benjamin Franklin, Berlin, Germany; Clinical Cooperation Group on Hematopoietic Stem Cell Transplantation, National Research Center for Environment and Health, Munich, Germany. Electronic address: armin.gerbitz@charite.de.
Hillemanns
Patrick
P
Department of Hematology and Oncology, Ludwig Maximilian University of Munich, Munich, Germany.
Schmid
Christoph
C
Department of Medicine II, Klinikum Augsburg, Augsburg, Germany.
Wilke
Andrea
A
Department of Hematology and Oncology, Ludwig Maximilian University of Munich, Munich, Germany; Clinical Cooperation Group on Hematopoietic Stem Cell Transplantation, National Research Center for Environment and Health, Munich, Germany.
Jayaraman
Rajshri
R
European School of Management and Technology ESMT, Schlossplatz, Berlin, Germany.
Kolb
Hans-Jochem
HJ
Department of Hematology and Oncology, Ludwig Maximilian University of Munich, Munich, Germany; Clinical Cooperation Group on Hematopoietic Stem Cell Transplantation, National Research Center for Environment and Health, Munich, Germany.
Eissner
Gunther
G
Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
Holler
Ernst
E
Department of Hematology and Oncology, University of Regensburg, Regensburg, Germany.
D018900:Dinucleotide Repeats; D018380:Hematopoietic Stem Cell Transplantation / Q000401:mortality*; D051547:Heme Oxygenase-1 / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D014019:Tissue Donors; D014184:Transplantation, Homologous
D051547:Heme Oxygenase-1