Association of FOXP3 Single Nucleotide Polymorphisms With Clinical Outcomes After Allogenic Hematopoietic Stem Cell Transplantation

Abstract

BackgroundForkhead box P3 (FOXP3) is an important marker of regulatory T cells. FOXP3 polymorphisms are associated with autoimmune diseases, cancers, and allograft outcomes. We examined whether single nucleotide polymorphisms (SNPs) at the FOXP3 locus are associated with clinical outcomes after allogenic hematopoietic stem cell transplantation (HSCT).MethodsFive FOXP3 SNPs (rs5902434, rs3761549, rs3761548, rs2232365, and rs2280883) were analyzed by PCR-sequencing of 172 DNA samples from allogenic HSCT patients. We examined the relationship between each SNP and the occurrence of graft-versus-host disease (GVHD), post-HSCT infection, relapse, and patient survival.ResultsPatients with acute GVHD (grades II-IV) showed higher frequencies of the rs3761549 T/T genotype, rs5902434 ATT/ATT genotype, and rs2232365 G/G genotype than did patients without acute GVHD (P=0.017, odds ratio [OR]=5.3; P=0.031, OR=2.4; and P=0.023, OR=2.6, respectively). Multivariate analysis showed that the TT genotype of rs3761549 was an independent risk factor for occurrence of acute GVHD (P=0.032, hazard ratio=5.6). In contrast, the genotype frequencies of rs3761549 T/T, rs5902434 ATT/ATT, and rs2232365 G/G were lower in patients with post-HSCT infection than in patients without infection (P=0.026, P=0.046, and P=0.031, respectively).Conclusionsrs3761549, rs5902434, and rs2232365 are associated with an increased risk of acute GVHD and decreased risk of post-HSCT infection.

The Role of Forkhead Box Proteins in Acute Myeloid Leukemia

“…SNPs have been identified as risk factors for AML development [115,116,117] and as prognostic factors in terms of survival outcomes and drug sensitivity/resistance [118,119,120,121]. FOXP3 SNPs have been recently identified as prognostic factors in pediatric and adult patients undergoing HSCT [122]. A comprehensive study of FOX family members SNPs may be another attractive and informative research field in AML.…”

Delayed NK Cell Reconstitution and Reduced NK Activity Increased the Risks of CMV Disease in Allogeneic-Hematopoietic Stem Cell Transplantation

“…Currently, preemptive therapy-based monitoring of CMV viremia is performed to improve CMV-related outcomes [5]. The range of CMV infection after HSCT can be different because HSCT patients have diverse CMV serostatus, different CMV prophylaxis, conditioning methods, genetic polymorphism, and inconstant post-HSCT immune reconstitution against CMV infection [5,7,9,11,12]. Considering these differences, CMV-specific immunity plays a vital role in controlling CMV reactivation and disease development.…”

Analysis of selected polymorphisms in FOXP3 gene in a cohort of Egyptian patients with schizophrenia

“…AA genotype of rs3761548 leads to loss of binding sites for TFs E47 and C-Myb [ 34 ]. Moreover, the GG genotype for rs2232365 and TT genotype for rs3761549 lead to loss of binding site for GATA3, activating enhancer-binding protein 4 (AP4) TFs, respectively [ 26 , 33 ]. The affection of FOXP3 protein in quality or quantity leads to Treg cell dysfunction and impairs the balance between Th1 and Th2 cells, disturbing the immune system’s balance toward the development of immunological and autoimmune diseases [ 41 ].…”

“…In HSCT, rs3761548 CC genotype was associated with veno-occlusive disease and cytomegalovirus (CMV) infection but no evidence of association with graft-versus-host disease (GVHD) or relapse [ 37 ]. Nam et al [ 33 ], on the other hand, did not find an association with allogenic HSCT outcomes. In renal transplantation, decreased overall surveillance was associated with rs361548 and rs2232365 mutant genotypes compared with the wild one [ 32 ].…”