title: Polymorphisms in TNFA and TNFR2 affect outcome of unrelated bone marrow transplantation.
abstract: Effects of polymorphisms in TNFA and TNFR2 on the outcome of 462 cases of unrelated bone marrow transplantation (uBMT) were studied retrospectively. Four alleles of TNFA (U01-U04) distinguished by polymorphism in the upstream region, -1031 (T/C), -863 (C/A) and -857 (C/T), and two alleles of TNFR2 (196M/196R) distinguished by polymorphism at codon 196 were determined. Transplantation involving TNFA-U02- and/or U03-positive donors and/or recipients resulted in a higher incidence of graft-versus-host disease (GVHD) of grade III-IV (P < 0.05 for donor type, P < 0.01 for recipient type) and a lower relapse rate than that involving TNFA-U01 homozygous recipients and/or donors (P < 0.025 for donor type, P < 0.01 for recipient type). These results include the HLA mismatching effect due to linkage disequilibirium of TNFA with HLA loci. However, the effects were also observed in HLA-A, -B and -DRB1 allele-matched transplantation. Transplantation from TNFR2-196R-positive donors exhibited a higher incidence of severe GVHD (P < 0.05) and tendency for a lower relapse rate than that from TNFR2-196M homozygous donors. TNFR2-196R of recipient origin had no effect on GVHD but increased the relapse rate (P < 0.025). These results suggest that TNFA and TNFR2 typings are helpful for predicting uBMT outcome and for preventing severe complications at an early stage.
authors.affiliation: Japanese Red Cross Central Blood Center, Tokyo, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: K
authors.initials: K
authors.lastname: Kashiwase
authors.forename: T
authors.initials: T
authors.lastname: Akaza
authors.forename: Y
authors.initials: Y
authors.lastname: Morishima
authors.forename: H
authors.initials: H
authors.lastname: Inoko
authors.forename: T
authors.initials: T
authors.lastname: Sasazuki
authors.forename: Y
authors.initials: Y
authors.lastname: Kodera
authors.forename: T
authors.initials: T
authors.lastname: Juji
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy; D015703:Antigens, CD / Q000235:genetics*; D016026:Bone Marrow Transplantation; D003062:Codon / Q000235:genetics; D005260:Female; D030342:Genetic Diseases, Inborn / Q000628:therapy; D005838:Genotype; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D019337:Hematologic Neoplasms / Q000628:therapy; D006648:Histocompatibility; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D016016:Proportional Hazards Models; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II; D012008:Recurrence; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D003062:Codon; D006680:HLA Antigens; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha