Objective: To explore the relationship between tumor necrosis factor (TNF) gene polymorphisms in donors and recipients and the incidence and severity of acute graft-versus-host diseases (aGVHD) after unrelated allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Methods: Single nucleotide polymorphisms (SNPs) of TNFalpha-238 (G/A), TNFalpha-857 (C/T), TNFalpha-863 (C/A), TNFalpha-1031 (T/C), TNFbeta + 252(A/G) were analyzed by Multiplex SNaPshot analysis in 76 pairs of donors and recipients.
Results: Transplantation involving donors with TNFalpha-857 CC genotype resulted in a higher incidence of grade II-IV aGVHD than donors with CT genotype (91.3% vs 8.7%, P = 0.039). In the 23 patients with grade II-IV aGVHD, no patients had TNFbeta + 252 AA genotype, 19 (82.6%) had GA genotype and 4 (17.4%) had GG genotype. There was a significant difference in the distribution pattern of the TNFbeta + 252 (AA, GA and GG) genotypes in these patients (P = 0.03). There was no significant association of TNFalpha-238 (G/A), TNFalpha-863 (C/A) and TNFalpha-1031(T/C) polymorphisms with the risk of aGVHD.
Conclusion: These results suggest donor TNFalpha-857 CC genotype is related to a higher incidence of grade II-IV aGVHD, and patients with TNFbeta + 252 AA genotype have protection against the risk of grade II-IV aGVHD.