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TNF Gene Polymorphism Associating With Acute Grafe-versus-host Disease In Unrelated Allogeneic Hematopoietic Stem Cell Transplants

Posted on:2010-07-25Degree:MasterType:Thesis
Country:ChinaCandidate:L JinFull Text:PDF
GTID:2144360275976996Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Allogeneic hematopoietic stem cell transplantation is the only cure method for many iseases.However,transplant related complications remain a major obstacle,in which acute graft-versus-host disease(aGVHD)is one of the most important problems. More recent observations have identified cytokine gene polymorphisms between patients and donors play potential roles in the occurrence and severity of graft-versus-host disease(GVHD).The present study aimed to determine existing associations between single nucleotide polymorphisms within TNF(tumor necrosis factor)α-238(G/A)(rs361525),TNFα-857(C/T)(rs1799724),TNF a-863(C/A)(rs1800630), TNFα-1031(T/C)(rs1799964),TNFβ+252(A/G)(rs909253)and acute graft-versus-host diseases(GVHD)after allogeneic unrelated hematopoietic stem cell transplantation.Polymorphisms were detected by polymerase chain reaction(PCR) using Multiplex SnaPshot.We found in the 23 patients with 2-4 grade acute GVHD, 21(91.3%)donors had the TNFα-857 CC genotype,2(8.7%)had the CT genotype.There was a significant difference in the distribution pattern of the CC and CT between donors with 0-1 grade and 2-4 grade acute GVHD(P=0.039).In the 23 patients with 2-4 grade acute GVHD,no patient had the TNFβ+252 AA genotype,19 (82.6%)had the GA genotype and 4(17.4%)had GG genotype.There was a significant difference in the distribution pattern of the AA,GA and GG genotypes in patients(P=0.03).The A-allele was observed significantly less often in 2-4 grade acute GVHD patients(P=0.03).Multivariate analysis identified TNFβ+252(A/G)as the only significant factor for 2-4 grade acute GVHD(Odds Ratio=3.616, P=0.022).In conclusion,TNFα-857(C/T)polymorphisms of donors and TNFβ+252(A/G)polymorphisms of patients are associated with 2-4 grade acute GVHD, These findings may improve patient outcome in the future by more clearly defining pathophysiological pathways,identify more suitable donors and clarify therapy on an individual patient basis.
Keywords/Search Tags:Allogeneic hematopoietic stem cell transplantation, tumor necrosis factor, cytokine gene polymorphism, graft-versus - host diseases
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