IL2 and TNFA gene polymorphisms and the risk of graft-versus-host disease after allogeneic haematopoietic stem cell transplantation.
This study aimed to analyse the association of gene polymorphisms with the outcome of allogeneic haematopoietic stem cell transplantation. We studied 122 donor/recipient pairs who received HLA-identical transplants from siblings at the Universidade Estadual de Campinas, Brazil, between June 1996 and June 2006. Donor/recipient alleles for TNFA-238 and IL2-330/+166 single-nucleotide polymorphisms (SNP) were analysed by PCR-SSP. No association was observed between the risk of acute graft-versus-host disease (GVHD) and these SNP. However, our findings suggest that the polymorphism of promoter gene TNFA-238GA is associated with the occurrence and severity of chronic GVHD. The probability of chronic GVHD in patients with GA genotype at position -238 of TNFA gene is 91.7% in contrast to 59.4% in patients with GG genotype (P = 0.038). In patients with donor GA genotype the probability of chronic GVHD is 90.8%, and 57.9% in patients with donor GG genotype (P = 0.038). The probability of extensive chronic GVHD in patients with TNFA-238GA is 91.7% compared with 46.3% in patients with TNFA-238GG (P = 0.0046). In patients with donor GA genotype at position -238 of the TNFA gene, it is 81.7%, compared with 44.5% in patients with donor GG genotype (P = 0.016). However, further studies with more patients are required to identify cytokine gene polymorphisms and their association with transplant-related complication in Brazil, particularly due to ethnic background, the relatively low power of detection of genetic markers of this study, and the complexity of the MHC region.
Viel
D O
DO
Laboratório de Imunogenética, Departamento de Análises Clínicas, Universidade Estadual de Maringá, Maringá, PR, Brazil.
Tsuneto
L T
LT
Sossai
C R
CR
Lieber
S R
SR
Marques
S B D
SB
Vigorito
A C
AC
Aranha
F J P
FJ
de Brito Eid
K A
KA
Oliveira
G B
GB
Miranda
E C M
EC
de Souza
C A
CA
Visentainer
J E L
JE
D000293:Adolescent; D000328:Adult; D001938:Brazil; D002648:Child; D005260:Female; D005838:Genotype; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D007376:Interleukin-2 / Q000235:genetics* / Q000276:immunology; D007938:Leukemia / Q000235:genetics / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000276:immunology; D035781:Siblings; D014019:Tissue Donors; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology
D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha