Association between cytokine gene polymorphisms and outcomes in renal transplantation: a meta-analysis of individual patient data

Thakkinstian, Ammarin; Дмитриенко, С. В.; Gerbase‐DeLima, Maria; McDaniel, D. Olga; Íñigo, Pablo; Chow, Kai Ming; McEvoy, Mark; Ingsathit, Atiporn; Trevillian, Paul; Barber, William H.; Attia, John

doi:10.1093/ndt/gfn185

Cited by 48 publications

(43 citation statements)

References 32 publications

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“…This has made these genes obvious potential triggers of acute and long-term rejection in transplantation, and after the HLA region are the most studied genes for a role in transplantation. Over the years, various cytokines and other immune response genes (see Table 1) have been investigated; however, a lack of consistent association of these genes with transplant survival has cast doubt over their potential role (as reviewed in the literatures 3,7,44,57,58 ).…”

Section: Cytokines and Other Immune Response Genesmentioning

confidence: 99%

“…Meta-analysis of variants within transforming growth factor-β 1 (TGF-β1), which is produced by all leukocytes and plays a key role in controlling inflammation, 59,60 from 5 different studies showed some evidence for association of a TGF-β1 codon 10 polymorphism (odds ratio, 1.51; 95% CI, 1.03-2.22) with poor graft outcomes. 57 Interestingly, genomewide association study (GWAS) screening for new susceptibility loci for diabetic nephrology in people with type 1 diabetes revealed genomewide significance for AFF3, which plays a role in TGF-β1-induced fibrosis in renal epithelial cells, providing further evidence for TGF-β1 pathways in renal dysfunction. 61 This suggests that although currently the role of cytokines in transplant outcomes remains uncertain, without further work, we cannot rule out a role for these variants in transplant survival.…”

Section: Hmox1mentioning

confidence: 99%

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Using Genetic Variation to Predict and Extend Long-term Kidney Transplant Function

Simmonds

2015

Transplantation

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Renal transplantation has transformed the life of patients with end-stage renal disease and other chronic kidney disorders by returning endogenous kidney function and enabling patients to cease dialysis. Several clinical indicators of graft outcome and long-term function have been established. Although rising creatinine levels and graft biopsy can be used to determine graft loss, identifying early predictors of graft function will not only improve our ability to predict long-term graft outcome but importantly provide a window of opportunity to therapeutically intervene to preserve graft function before graft failure has occurred. Since understanding the importance of matching genetic variation at the HLA region between donors and recipients and translating this into clinical practise to improve transplant outcome, much focus has been placed on trying to identify additional genetic predictors of transplant outcome/function. This review will focus on how candidate gene studies have identified variants within immunosuppression, immune response, fibrotic pathways, and specific ethnic groups, which correlate with graft outcome. We will also discuss the challenges faced by candidate gene studies, such as differences in donor and recipient selection criteria and use of small data sets, which have led to many genes failing to be consistently associated with transplant outcome. This review will also look at how recent advances in our understanding of and ability to screen the genome are starting to provide new insights into the mechanisms behind long-term graft loss and with it the opportunity to target these pathways therapeutically to ultimately increase graft lifespan and the associated benefits to patients.

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Section: Cytokines and Other Immune Response Genesmentioning

confidence: 99%

Section: Hmox1mentioning

confidence: 99%

Using Genetic Variation to Predict and Extend Long-term Kidney Transplant Function

Simmonds

2015

Transplantation

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“…Thakkinstian and colleagues attempted to achieve individual patient data for their meta-analysis in the kidney transplant setting by petitioning authors [55]. Five of 13 invited authors collaborated: these thirteen papers had passed pre-determined selection criteria.…”

Section: Meta-analyses Of Published Associationsmentioning

confidence: 99%

Genetic polymorphisms in the immune response: A focus on kidney transplantation

Stojanova

Pouché

Picard

2016

Clinical Biochemistry

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“…Interestingly, OT patients seem to be low responders to blood transfusions, reinforcing the idea of genetic predisposition to alloimmunization [118]. The physiological mechanism of tolerance in transplantation may involve regulatory T cells, pDCs and mDCs ratio, LTδ, as well as some cytokine polymorphisms, especially in TGF and IL-10 [119,120]. However, no sensitive and specific marker has been clearly identified, and it is difficult to discriminate between causal factors and consequences.…”

Section: Operational Tolerance (Ot) In Transplantationmentioning

confidence: 99%

From Donor to Recipient: Current Questions Relating to Humoral Alloimmunization

et al. 2014

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Alloimmunization is an undesirable iatrogenic effect of transfusion and transplantation. In fact, recipients can be considered as responders or not responders, in a continuum from tolerance, including organ transplantation and transfusion, to polyimmunized and refractory patients. New models and large studies have enabled a better understanding of the mechanisms that induce specific alloantibody (alloAb) generation. Here, we focus on risk factors of alloimmunization. We review the alloantibody characteristics, summarize the different leukocytes involved in their induction, and suggest some hypotheses.

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Association between cytokine gene polymorphisms and outcomes in renal transplantation: a meta-analysis of individual patient data

Abstract: Pooled results to date suggest possible association between both the TGF-beta1 c10 polymorphism and a 3-SNP-haplotype of IL-10 and poor outcomes in renal transplantation, but this needs to be confirmed in larger studies.

Cited by 48 publications

References 32 publications

Using Genetic Variation to Predict and Extend Long-term Kidney Transplant Function

Using Genetic Variation to Predict and Extend Long-term Kidney Transplant Function

Genetic polymorphisms in the immune response: A focus on kidney transplantation

From Donor to Recipient: Current Questions Relating to Humoral Alloimmunization

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