Genetic variants of FOXP3 influence graft survival in kidney transplant patients |
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| Authors: | Anja U. Engela Karin Boer Joke I. Roodnat Annemiek M.A. Peeters Paul H. Eilers Judith A. Kal-van Gestel Fernando Rivadeneira Willem Weimar Carla C. Baan |
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| Affiliation: | 1. Department of Internal Medicine, Transplantation Laboratory, Erasmus University Medical Center, Rotterdam, The Netherlands;2. Department of Internal Medicine, Nephrology, Erasmus University Medical Center, Rotterdam, The Netherlands;3. Department of Biostatistics, Erasmus University Medical Center, Rotterdam, The Netherlands;4. Department of Internal Medicine, Endocrinology Laboratory, Erasmus University Medical Center, Rotterdam, The Netherlands;5. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands |
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| Abstract: | FOXP3+ regulatory T cells (Treg) play a role in controlling alloreactivity. It has been shown that short (GT)n dinucleotide repeats (?(GT)15; S) in the promoter region of the FOXP3 gene enhance the promoter activity when compared to long (GT)n repeats (?(GT)16; L). The present study retrospectively investigated the influence of this (GT)n FOXP3 gene polymorphism on renal allograft survival. A total of 599 consecutive first-time kidney transplant patients (median follow-up time 7.7 years) were subdivided according to their FOXP3 genotype into the S-genotype group (SG) and the L-genotype group (LG). The SG was superior to the LG in both general graft survival censored for death (logrank test, p = 0.013) and graft survival following acute rejection (p = 0.021). Multivariate analysis defined the (GT)n FOXP3 dinucleotide repeat polymorphism as an independent factor and confirmed an advantage for the SG in renal allograft survival (HR = 0.67, 95% CI 0.48–0.94, p = 0.02). This gene association study identified a beneficial effect of FOXP3 genetic variants on graft survival in kidney transplant patients. |
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| Keywords: | AR, acute rejection DD, deceased donor F, female FAM, 6-carboxyfluorescein FOXP3, forkhead/winged helix box P3 GF, graft failure GLM, generalized linear model HI, highly immunized HLA, human leukocyte antigen I, immunized IB, immunological background IF/TA, interstitial fibrosis and tubular atrophy IPEX, immunodysregulation polyendocrinopathy enteropathy X-linked syndrome IRI, ischemia&ndash reperfusion injury KTx, kidney transplantation L, long (GT)n dinucleotide repeats LD, living (un-)related donor LG, L-genotype group M, male NI, non-immunized NIB, non-immunological background PBMC, peripheral blood mononuclear cells PRA, panel reactive antibody RA, rheumatoid arthritis S, short (GT)n dinucleotide repeats SG, S-genotype group SLE, systemic lupus erythematosus SNP, single nucleotide polymorphism Treg, regulatory T cell XCI, X-chromosome inactivation |
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