IL-2 and TNF-alpha promoter polymorphisms in patients with acute kidney graft rejection
ABSTRACT Proinflammatory cytokines have been implicated in the pathogenesis of acute kidney allograft rejection. The aim of the study was to examine the association between interleukin (IL)-2 -330 and tumor necrosis factor (TNF)-alpha -308 promoter polymorphisms and acute kidney allograft rejection.
The study included 72 patients with long-term stable graft function, and 57 diagnosed with acute kidney allograft rejection.
Patients with acute kidney allograft rejection showed a prevalence of subjects with TNF-alpha T2 allele (P < .05). The risk of acute kidney allograft rejection diagnosis was 2.5-fold greater among carriers of the T2 allele than those homozygous for T1T1 (OR 2.53, 95% CI 1.19 to 5.37, P < .05) There was no statistically significant difference in the distribution of IL-2 genotypes between patients with stable graft function and acute kidney allograft rejection.
The results suggest that TNF-alpha-308 promoter polymorphism is a risk factor for acute kidney allograft rejection.
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ABSTRACT: Background: Vascular endothelial growth factor (VEGF) is a cytokine which plays an important role in the division, proliferation and migration of endothelial cells. In the kidney, VEGF expression is found in glomerular podocytes and in tubular epithelial cells, which may result in acute inflammatory reactions. Methods: The role of VEGF gene polymorphisms (-2578 C/A, -2549 18 bp Ins/Del, -1154 G/A and +936 C/T) was investigated in 272 patients who underwent renal transplantation. ARMS-PCR and PCR-RFLP were used. Patients were categorized into acute allograft rejection (n = 76) and nonrejection (n = 196). Results: The VEGF -1154 GG genotype and the +936 T allele were found to be susceptible to acute rejection (AR). T-A-A-I, T-A-A-D, T-G-C-I and C-A-A-I haplotypes revealed a predisposition among AR cases. In silico analysis revealed +936 T as a significant allele involved in the transcription regulation. Conclusion: These results highlight the role of VEGF polymorphisms in acute allograft rejection. © 2015 S. Karger AG, Basel.Nephron 01/2015; 129(2). DOI:10.1159/000368700 · 13.26 Impact Factor
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ABSTRACT: Infection and rejection are common complications faced by lung transplant recipients (LTRs), and have become major impediments to long-term survival. Cytokine may play an important role in the development of these complications. In this study, we explored the correlation between TNF-α (-308 A/G), TGF-β1 (+869 T/C, +915 G/C), IL-10 (-592 C/A, -819 T/C, -1082 G/A), IL-6 (-174 G/C) and IFN-γ (+874 T/A) gene polymorphisms and the incidence of acute rejection and infection. Transplant outcomes were reviewed in a retrospective cohort of 113 LTRs from a single center between December 2004 and November 2012. Cytokine polymorphisms were measured using sequence-specific primer-based PCR. HLA typing was performed for the donors and recipients. We found that the LTRs with the IL-10 -819 CC and -592 CC genotypes had a significantly decreased risk of infection (p=0.017, OR=0.177, 95% CI=0.04-0.85). However, we found no significant association between cytokine polymorphisms and acute rejection. Furthermore, the data revealed the occurrence of acute rejection was strongly associated with infection episodes (χ(2) =8.5256, p<0.01). These results suggest that LTRs possessing the IL-10 -819 CC and -592 CC genotype may be protected from the occurrence of infection. Our results demonstrated that infection is an important cause of acute rejection for LTRs. This article is protected by copyright. All rights reserved.Clinical Transplantation 06/2014; 28(9). DOI:10.1111/ctr.12411 · 1.49 Impact Factor
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ABSTRACT: Patient genetic make-up may contribute to a higher risk for acute rejection episodes (AREs). Because interleukin-2 (IL2) and IL2 receptor β (IL2RB) play key roles in immune modulation, we investigated the effect of single-nucleotide polymorphisms (SNPs) in the IL2 gene (rs2069762; T>G, promoter; and rs2069763; G>T, exon 1, Leu38Leu) and IL2RB gene (rs228942: C>A, exon 1, Asp391Glu; and rs228953: C>T, exon 8, Gly250Gly) on renal ARE risk in 61 ARE patients and 276 control renal allograft recipients in Korea. The genotype frequencies of the IL2 and IL2RB SNPs showed Hardy-Weinberg equilibrium in both ARE and control groups. No significant difference in the genotype frequencies of the 2 IL2 SNPs was detected between non-ARE and ARE subjects (P > .05). The occurrence of AREs was significantly associated with genetic variants of the IL2RB gene (rs228942: odds ratio [OR] 2.11, 95% confidence interval [CI] 1.19-3.74; P = .0096, dominant model; rs228953: OR 1.58, 95% CI 1.04-2.38; P = .029, codominant model). In the haplotype-based analysis, the AC haplotype of IL2RB (χ(2) = 4.738; P = .0295) showed associations with ARE. Our results demonstrate that genetic variants of IL2RB may be associated with the development of AREs and may help predict ARE risk in kidney transplantation patients.Transplantation Proceedings 07/2011; 43(6):2383-7. DOI:10.1016/j.transproceed.2011.06.014 · 0.95 Impact Factor