‐174G/C interleukin‐6 gene polymorphism and the risk of transplanted kidney failure or graft loss during a 5‐year follow‐up period

Abstract

The influence of cytokine gene polymorphisms on transplanted kidney outcome is not well understood. The aim of this one-centre study was to analyse the association between tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-10, interferon-γ (IFN-γ) and transforming growth factor-β1 (TGF-β1) genotypes and the incidence of delayed graft function (DGF), acute rejection (AR) and 5-year kidney graft loss. Genotyping was performed in 199 subsequent kidney graft recipients from deceased donors without induction therapy based on polymerase chain reaction method using sequence-specific primers for TNF-α (-308A/G), IL-10 (-1082A/G, -819T/C and -592A/C), IL-6 (-174G/C), IFN-γ (+874T/A) and TGF-β1 (in codons 10T/C and 25G/C). Genotypes were grouped according to the strength of cytokine expression. During a 5-year follow-up period, 14 patients died with functioning graft and 33 developed graft failure. The analysed polymorphisms were not associated with the incidence of DGF. The frequency of early episodes of AR was significantly associated only with TGF-β1 genotype. There was an association between -174G/C IL-6 gene polymorphism and the death-censored kidney graft survival. The risk of graft loss during 5-year follow-up period was greater by 57% for GG or GC (higher IL-6 production) than for CC carriers. None of the other analysed polymorphisms significantly influenced both patients and kidney graft survival, also in the analysis of the subgroup with human leucocyte antigen-DR mismatch. -174G/C IL-6 genotype of the kidney graft recipient could modulate the rate of graft excretory function deterioration and the risk of graft loss by influencing their constitutional expression.

Impact of Immune-Modulatory Drugs on Regulatory T Cell

“…In transplantation, blocking IL-6 leads to decreased IFN-γ and IL-17 mRNA, reduced alloantigen-stimulated T cell proliferation, increased proportion of Treg, and prolonged allograft survival in mouse models 202-204 . In humans, IL-6 is associated with acute and chronic rejections and IL-6 levels correlate with the degree of inflammation in the allografts 205-210 . The use of tocilizumab with intravenous immunoglobulin in sensitized kidney transplant patients shows improved donor-specific antibody levels similar to the results obtained in a mouse model 211,212 .…”

Recipient IL-6-572C/G genotype is associated with reduced incidence of acute rejection following liver transplantation

“…28 Studies on the impact of recipient À174 G/C polymorphism on acute rejection following renal transplantation have provided conflicting results. One study found a lower frequency of G/G or G/C genotype in recipients who developed acute rejection, 29 while another found a higher frequency of these genotypes, 30,31 although the results of these studies were not statistically significant. High levels of the G/G and G/C IL-6 promoter genotypes have been shown to be significantly associated with decreased risk of acute rejection following liver transplant.…”

Combined Effects of TGFB1 +869 T/C and +915 G/C Polymorphisms on Acute Rejection Risk in Solid Organ Transplant Recipients: A Systematic Review and Meta-Analysis

“…As for ethnicity, 7 were studies of Caucasians [9], [22], [23], [27], [28], [37], 3 studies were of Asians [19]–[21], and 4 studies of mixed ethnicity [13], [18], [26], [29]. Regarding the immunosuppressive protocols, patients were uniformly prescribed with CsA in 5 studies[18]–[20], [23], [29] while in the remaining 9 studies were applied with either CsA or FK506[9], [13], [21], [22], [24]–[28] (Table 1). …”