The IFN-γ Allele Is Correlated to Moderate-to-Severe Acute Graft-Versus-Host Disease After Allogeneic Stem Cell Transplant

Abstract

Objectives: 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-ß T+869C, IL-4 C-590T, and IFN-γ T+874A cytokines in bone marrow transplant patients.

Materials and Methods: The Amplification refractory mutation system-polymerase chain reaction ARMS-PCR method was used to characterize IL-6 G-174C, TGF-ß T+869C, and IFN-γ 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-γ +874T allele (P = .027, OR=0.198, 95% CI=0.049-0.801) was correlated to moderate-to-severe graft-versus-host disease. TGF-ß T+869C, IFN-γ 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).

Conclusion: According to the results, we concluded that the IFN-γ T+874A gene polymorphism has a predictive value for severity of graft-versus-host disease after bone marrow transplant. High producer genotypes of IFN-γ are genetic risk factors for development of graft-versus-host disease.