Ann Lab Med.  2018 Nov;38(6):591-598. 10.3343/alm.2018.38.6.591.

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

• Nam M
• Shin S
• Park KU
• Kim I
• Yoon SS
• Kwon TK
• Song EY

• KMID: 2429126
• DOI: http://doi.org/10.3343/alm.2018.38.6.591

Abstract

BACKGROUND
Forkhead 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).
METHODS
Five 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.
RESULTS
Patients 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).
CONCLUSIONS
rs3761549, rs5902434, and rs2232365 are associated with an increased risk of acute GVHD and decreased risk of post-HSCT infection.

Keyword

Allogenic hematopoietic stem cell transplantation; FOXP3; Graft-versus-host disease; Infection; Polymorphism

MeSH Terms

Allografts
Autoimmune Diseases
DNA
Genotype
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation*
Hematopoietic Stem Cells*
Humans
Multivariate Analysis
Odds Ratio
Polymorphism, Single Nucleotide*
Recurrence
Risk Factors
T-Lymphocytes, Regulatory
DNA

Figure

• 

  Fig. 1 Impact of the FOXP3 polymorphism on acute GVHD occurrence after allogenic HSCT. (A) rs5902434, (B) rs3761549, (C) rs3761548, (D) rs2232365, and (E) rs2280883. Recipients with rs3761549 TT genotype showed higher cumulative incidence of acute GVHD than recipients with rs3761549 CC or CT genotype (P=0.023).Abbreviations: FOXP3, Forkhead box P3; GVHD, graft-versus-host disease; HSCT, hematopoietic stem cell transplantation.

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