The IFN-gamma allele is correlated to moderate-to-severe acute graft-versus-host disease after allogeneic stem cell transplant.
OBJECTIVE
Analysis of nonhistocompatibility leucocyte antigen functional genomics in stem cell transplant can lead to prediction of clinical outcomes in histocompatibility leucocyte antigen-matched sibling-transplant recipients. Some of the cytokine gene polymorphisms might be associated with severe, acute graft-versus-host disease after allogeneic stem cell transplant. We evaluated gene polymorphisms of IL-6 G-174C, TGF-beta T+869C, IL-4 C-590T, and IFN-alpha T+874A cytokines in bone marrow transplant patients.


METHODS
The amplification refractory mutation system-polymerase chain reaction ARMSPCR method was used to characterize IL-6 G-174C, TGF-beta T+869C, and IFN-alpha T+874A polymorphisms, and PCR-RFLP, using AvaII restriction enzyme, was done for IL-4 C-590T characterization in 35 bone marrow transplant patients. Acute graft-versus-host disease episodes were diagnosed according to EMBT criteria.


RESULTS
Analysis showed that IFN-alpha +874T allele (P = .027, OR=0.198, 95% CI=0.049-0.801) was correlated to moderate-to-severe graft-versus-host disease. TGF-beta T+869C, IFN-alpha T+874A, IL-6 G-174C and IL-4 C-590T frequencies were not significantly different in the 2 graft-versus-host disease severity groups (P > .05).


CONCLUSIONS
According to the results, we concluded that the IFN-alpha T+874A gene polymorphism has a predictive value for severity of graft-versus-host disease after bone marrow transplant. High producer genotypes of IFN-alpha are genetic risk factors for development of graft-versus-host disease.
Karimi
Mohammad Hossein
MH
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Daneshmandi
Saeed
S
Pourfathollah
Ali Akbar
AA
Geramizadeh
Bita
B
Ramzi
Mani
M
Yaghobi
Ramin
R
Ebadi
Padideh
P
D000208:Acute Disease; D016009:Chi-Square Distribution; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007492:Iran; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D016212:Transforming Growth Factor beta / Q000235:genetics; D014184:Transplantation, Homologous; D016896:Treatment Outcome
C508598:IL4 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma