Polymorphisms of transforming growth factor-beta1 and transforming growth factor-beta1 type II receptor genes are associated with acute graft-versus-host disease in children with HLA-matched sibling bone marrow transplantation.
The aim of this study was to determine whether the gene polymorphisms of Th1/Th2 and immunoregulatory cytokines were associated with aGVHD in Japanese children receiving allogeneic bone marrow transplantation (allo BMT). We investigated polymorphisms of genes encoding interleukin (IL)-4, IL-4 receptor (IL-4 R), IL-10, transforming growth factor (TGF)-beta1, TGF-beta1 type II receptor (TGF-beta1 RII), interferon (IFN)-gamma, IFN-gamma type 2 receptor (IFN-gamma R2), and IFN regulatory factor (IRF)-1. Sixty-seven patients were treated with allo BMT from HLA-identical siblings, and aGVHD was observed in 38. TGF-beta1 codon 10 leucine (Leu) /proline (Pro) polymorphism in donors was associated with the development of aGVHD. Patients having donors with the Pro allele had aGVHD more frequently than those without Pro allele (30/45 vs 8/20, odds ratio = 3.00; P = 0.04). TGF-beta1 RII 1167 C/T polymorphism in recipients was also associated with the development of aGVHD. The incidence was significantly higher in recipients with T allele than in those without T allele (21/27 vs 16/35, odds ratio = 4.16; P = 0.01). In conclusion, genetic backgrounds of TGF-beta1 and TGF-beta1 RII may be involved in the development of aGVHD in HLA-matched sibling BMT in Japanese children.
Hattori
H
H
Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Matsuzaki
A
A
Suminoe
A
A
Ihara
K
K
Nagatoshi
Y
Y
Sakata
N
N
Kawa
K
K
Okamura
J
J
Hara
T
T
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000235:genetics; D005260:Female; D006086:Graft vs Host Disease / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018121:Receptors, Cytokine / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D035781:Siblings; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic
D016207:Cytokines; D018121:Receptors, Cytokine; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II