Ann Lab Med.  2017 Sep;37(5):420-425. 10.3343/alm.2017.37.5.420.

Association of Foxp3 Polymorphism With Allograft Outcome in Kidney Transplantation

Affiliations
  • 1Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea. eysong1@snu.ac.kr
  • 2Department of Laboratory Medicine, Seegene Medical Foundation, Seoul, Korea.
  • 3Transplantation Center, Seoul National University Hospital, Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Abstract

BACKGROUND
Forkhead box P3 (Foxp3) is the most reliable marker for regulatory T cells, which play an important role in maintaining renal allograft tolerance. Recently, Foxp3 polymorphisms have been reported to be associated with graft outcome in kidney transplantation. We analyzed the association of Foxp3 polymorphisms with renal allograft outcome.
METHODS
Foxp3 polymorphisms (rs3761548 A/C, rs2280883 C/T, rs5902434 del/ATT, and rs2232365 A/G) were tested by PCR with sequence-specific primers (PCR-SSP) in 231 adult kidney transplantation recipients from 1996-2004 at Seoul National University Hospital.
RESULTS
Patients with the rs3761548 CC genotype showed better graft survival than those with the AC or AA genotype (log rank test, P=0.03). Patients with the rs3761548 CC genotype also showed a lower rate of recurrence of the original glomerular disease than those with the AC or AA genotype (P=0.01). The frequency of acute rejection (AR) in patients with the rs2280883 TT genotype was lower than that in patients with the rs2280883 CT or CC genotype (26.9% vs 53.3%, P=0.038). Patients with the rs2280883 TT genotype also showed better graft survival than those with the CT or CC genotype (P=0.03).
CONCLUSIONS
Foxp3 rs3761548 CC and rs2280883 TT genotypes were associated with superior graft outcome of kidney transplantation. Further studies involving a larger number of patients are needed.

Keyword

Foxp3; Single nucleotide polymorphism; Kidney transplantation; Graft outcome

MeSH Terms

Adult
Allografts*
Genotype
Graft Survival
Humans
Kidney Transplantation*
Kidney*
Polymerase Chain Reaction
Polymorphism, Single Nucleotide
Recurrence
Seoul
T-Lymphocytes, Regulatory
Transplantation Tolerance
Transplants

Figure

  • Fig. 1 Kaplan-Meier survival analysis of graft survival according to Foxp3 polymorphisms. (A) Patients with rs3761548 CC genotype (n=209) showed better graft survival than those with AC or AA genotype (n=22) (log rank test, P=0.03). (B) Patients with rs2280883 TT genotype (n=216) showed better graft survival than those with CT or CC genotype (n=15) (P=0.02).

  • Fig. 2 Kaplan-Meier survival analysis of recurrence of original glomerular disease post kidney transplantation according to Foxp3 polymorphism rs3761548.


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