Association between IL-6 –174G/C polymorphism and acute rejection of renal allograft: Evidence from a meta-analysis

Lv, Ruixue; Hu, Xiuying; Bai, Yi; Long, Hongyu; Xu, Luhang; Liu, Zhenhua; Xiao, Li; Huang, He; Wang, Lanlan; Ying, Binwu

doi:10.1016/j.trim.2011.10.003

Cited by 21 publications

(18 citation statements)

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“…Many studies have investigated the association between cytokine gene polymorphisms and acute renal graft rejection, with different studies reporting different results. [1,3,5,17–25] The variable clinical diagnostic processes, different PRA, HLA match status, immunosuppressive protocols, small sample size, and ethnicity may be the main reasons for the inconsistent results of different studies [26,27]. …”

Section: Discussionmentioning

confidence: 99%

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Xie

Wan

2016

Med Sci Monit

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BackgroundAcute rejection (AR) after renal transplantation affects both patient and graft survival. There is growing evidence of the genetic association between cytokine or its receptor antagonist and AR in solid organ transplantation. The objectives of this study were to investigate the role of recipient TNF β, IL-10, IL-1β, and IL-1 receptor antagonist (ra) gene polymorphism, as well as traditional clinical variables such as panel-reactive antibody (PRA) levels, donor type, and HLA mismatches in AR following renal transplantation.Material/MethodsTNF β (+252A/G), IL-10 (−592A/C), IL-1β (−511C/T) and IL-1ra (86 bp VNTR) gene polymorphisms were determined in 195 renal allograft recipients with and without AR, using PCR. Both these genotypic variants and clinical risk factors were investigated for correlation with AR within the first year after renal transplantation.ResultsPatients with increased pre-transplant PRA levels (P<0.001) and donor type (P=0.012) were prone to the development of AR. After adjusting for all variables of P<0.2, a PRA level >10% (OR=4.515, 95% confidence intervals=1.738–11.727, P=0.002) and the receipt of a graft from a donation after cardiac death (DCD) donor (OR=2.437, 95% confidence intervals=1.047–5.673, P=0.039) remained significantly associated with AR in a multivariate logistic regression analysis. No correlation could be found between recipients with an episode and absence of acute rejection and the gene polymorphisms of these cytokines investigated in the present study.ConclusionsThis study shows that the presence of increased pre-transplant levels of PRA and the receipt of a graft from DCD donor other than cytokine gene polymorphisms are significant risk factors for AR in renal transplantation. To reduce the occurrence of AR, clinicians should take necessary measures to lower the PRA levels and pay more attention to patients who received a graft from a DCD donor.

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Section: Discussionmentioning

confidence: 99%

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Xie

Wan

2016

Med Sci Monit

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“…While several case-control studies have been conducted with large organ transplant cohorts, the identification of genotype/phenotype associations has been limited to the discoveries of polymorphisms with small effect, that have been reviewed in (16) , which have often not been replicated (17–19) . Such studies have observed small average effects measured across groups of transplants when our study is measuring moderate effects in individual transplants.…”

Section: Discussionmentioning

confidence: 99%

Exome Sequencing and Prediction of Long-Term Kidney Allograft Function

Laurent

Muthukumar

Burbach

et al. 2015

Preprint

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Current strategies to improve graft outcome following kidney transplantation consider information at the human leukocyte antigen (HLA) loci. Cell surface antigens, in addition to HLA, may serve as the stimuli as well as the targets for the anti-allograft immune response and influence long-term graft outcomes. We therefore performed exome sequencing of DNA from kidney graft recipients and their living donors and estimated all possible cell surface antigens mismatches for a given donor/recipient pair by computing the number of amino acid mismatches in trans-membrane proteins. We designated this tally as the allogenomics mismatch score (AMS). We examined the association between the AMS and post-transplant estimated glomerular filtration rate (eGFR) using mixed models, considering transplants from three independent cohorts (a total of 53 donor-recipient pairs, 106 exomes, and 239 eGFR measurements). We found that the AMS has a significant effect on eGFR (mixed model, effect size across the entire range of the score: -19.4 [-37.7, -1.1], P = 0.0042, χ2 = 8.1919, d.f. = 1) that is independent of the HLA-A, B, DR matching, donor age, and time post-transplantation. The AMS effect is consistent across the three independent cohorts studied and similar to the strong effect size of donor age. Taken together, these results show that the AMS, a novel tool to quantify amino acid mismatches in trans-membrane proteins in individual donor/recipient pair, is a strong, robust predictor of long-term graft function in kidney transplant recipients.PLOS Computational Biology |

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“…Thirdly, some additional SNPs, e.g. IL6 -174G > C (rs1800795) and IL10 -592C > A (Lv et al,2012;Xiong et al,2015) were not included in this study because of incompatibility with the genotyping array, and insufficient DNA was available to carry out separate genotyping of these SNPs. In addition, other important innate immune genes, e.g.…”

Section: Discussionmentioning

confidence: 99%

No Major Effect of Innate Immune Genetics on Acute Kidney Rejection in the First 2 Weeks Post-Transplantation

Barratt

Coller

et al. 2020

Front. Pharmacol.

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Objective: To investigate the effect of recipient and donor CASP1, CRP, IL1B, IL2, IL6, IL6R, IL10, MYD88, TGFB, TLR2, TLR4, and TNF genetics on acute kidney rejection in the first 2 weeks post-transplant in TAC-treated kidney transplant recipients.Methods: This study included 154 kidney transplant recipients and 81 donors successfully genotyped for 17 polymorphisms in these genes. All recipients were under triple immunosuppressant therapy of TAC, mycophenolate mofetil, and prednisolone. Recipient and donor genotype differences in acute rejection incidence within the first 2 weeks post-transplantation were assessed by logistic regression, adjusting for induction therapy, human leukocyte antigen mismatches, kidney transplant number, living donor, and peak panel-reactive antibody scores.Results: A trend (Cochran-Armitage P = 0.031) of increasing acute rejection incidence was observed from recipient IL6 -6331 T/T (18%) to T/C (25%) to C/C (46%) genotype [C/C versus T/T odds ratio (95% confidence interval) = 6.6 (1.7 to 25.8) (point-wise P = 0.017)]. However, no genotype differences were significant after Bonferroni correction for multiple comparisons.Conclusions: This study did not detect any statistically significant effects of recipient or donor innate immune genetics on acute rejection incidence in the first 2 weeks posttransplantation. However, the sample size was small, and future larger studies or Frontiers in Pharmacology | www.frontiersin.org

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Association between IL-6 –174G/C polymorphism and acute rejection of renal allograft: Evidence from a meta-analysis

Cited by 21 publications

References 43 publications

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Association Between Cytokines and Their Receptor Antagonist Gene Polymorphisms and Clinical Risk Factors and Acute Rejection Following Renal Transplantation

Exome Sequencing and Prediction of Long-Term Kidney Allograft Function

No Major Effect of Innate Immune Genetics on Acute Kidney Rejection in the First 2 Weeks Post-Transplantation

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