Relationship between cytotoxic T‐lymphocyte antigen 4 ‐318C/T (rs5742909) gene polymorphism and the risk of acute rejection in renal transplantation

Yang, Chunhua; Chen, Xue-Xia; Chen, Li; Zheng, Danping; Liu, Qiong-Shan; Xie, Wei; Zhou, Tian-Biao; Drummen, Gregor P. C.

doi:10.1111/petr.12920

Cited by 5 publications

(6 citation statements)

References 22 publications

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“…Fifth, we cannot exclude that CTLA-4 polymorphic variants other than rs231775 might play a role as genetic predictive factors for acute renal rejection. In this regard, it should be noted that a number of meta-analyses have been published on the association between other polymorphisms of CTLA-4 and acute renal rejection 20 – 22 , 58 , 59 , however none of these studies applied TSA or FPRP for convincing evidence of an association between these additional CTLA-4 SNPs and acute renal allograft rejection. Finally, the lack of informative data in the identified studies precluded the possibility to adjust ORs for clinical confounding factors, and to investigate interaction effects of rs231775 with other polymorphic gene variants of CTLA-4.…”

Section: Discussionmentioning

confidence: 99%

“…CTLA-4 exerts its immunosuppressive function through a variety of mechanisms which include competition with the co-stimulatory CD28 molecule for binding to their shared B7 ligands (CD80/CD86) on the antigen-presenting cells (APC) 2 , and interference with TCR-mediated signal transduction 3 . Given the key role of CTLA4 on regulation of allograft rejection and tolerance 4 , 5 , a great attention has been focused on the relationship between CTLA-4 genetic variation and graft outcome following solid organ transplantation 6 – 9 .…”

Section: Introductionmentioning

confidence: 99%

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CTLA-4 rs231775 and risk of acute renal graft rejection: an updated meta-analysis with trial sequential analysis

Cargnin

Galli

Smıth

et al. 2020

Sci Rep

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Contrasting results exist on the association between CTLA-4 rs231775 and acute rejection in kidney transplant recipients. We herein conducted an updated systematic review with meta-analysis and trial sequential analysis (TSA) to clarify this relationship and to establish whether the current evidence is sufficient to draw firm conclusions. In addition, noteworthiness of significant pooled odds ratios (ORs) was estimated by false positive report probability (FPRP). A comprehensive search was performed through PubMed, Web of Knowledge, Cochrane Library and Open Grey up to October 2019. Fifteen independent cohorts, including a total of 5,401 kidney transplant recipients, were identified through the systematic review. Overall, no association was detected with the allelic (OR 1.07, 95% CI 0.88–1.30, P = 0.49), dominant (OR 0.94, 95% CI 0.73–1.22, P = 0.66) or the recessive (OR 1.18, 95% CI 0.97–1.43, P = 0.096) model of CTLA-4 rs231775. In each genetic model, the cumulative Z-curve in TSA crossed the futility boundary and entered the futility area. In addition, none of the significant genetic comparisons detected in the subsequent and sensitivity analyses or in previously reported meta-analyses were found to be noteworthy by FPRP. In conclusion, this study provides strong evidence that CTLA-4 rs231775 is not a clinically-relevant genetic risk determinant of acute rejection after renal transplantation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CTLA-4 rs231775 and risk of acute renal graft rejection: an updated meta-analysis with trial sequential analysis

Cargnin

Galli

Smıth

et al. 2020

Sci Rep

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“…The associations have further been disproved by two comprehensive, independent meta-analyses, which both had over 2000 cases analysed; one investigated both +49 and −318 (2081 cases), and the other focused solely on the −318 polymorphism (2356 cases) [ 56 , 57 ].…”

Section: Ctla4 Gene Polymorphisms and Solid Orgmentioning

confidence: 99%

The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation

Rosik

Szostak

Machaj

et al. 2021

IJMS

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HLA matching, transplantation technique, or underlying disease greatly influences the probability of long-term transplantation success. It has been hypothesised that genetic variation affecting antigen presentation also contributes to the outcomes of both solid organ transplantation and allogeneic haematopoietic stem cell transplantation (AHSCT). Those genes, along with those responsible for innate and adaptive immunity, have become targets of investigation. In this review, we focus on the role of CTLA4 in the process of acute graft rejection and summarise the progress in our understanding of its role in predicting the outcome. We present the results of the latest studies investigating the link between CTLA4 gene variability and AHSCT, as well as organ transplantation outcomes. While some studies found a link between +49 A/G and -318 C/T and transplantation outcomes, comprehensive meta-analyses have failed to present any association. The most recent field reviews suggest that the -1772 T/C (rs733618) CC genotype is weakly associated with a lower risk of acute graft rejection, while +49 A/G might be clinically meaningful when investigated in the context of combinations with other polymorphisms. Studies verifying associations between 12 CTLA4 gene SNPs and AHSCT outcomes present inexplicit results. Some of the most commonly studied polymorphisms in this context include +49 A/G (rs231775) and CT60 A/G (rs3087243). The results signify that, in order to understand the role of CTLA4 and its gene polymorphisms in transplantology, further studies must be conducted.

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“…Prethodne studije su pokazale ključnu inhibitornu ulogu CTLA-4 molekula, kao i infekcije, limfocitnu infiltraciju i hipogamaglobulinemiju kao samo neke od mogućih posljedica u slučaju mutacije u okviru CTLA4 gena (22). Rezultati metaanalize, sprovedene 2017. godine, ukazali su na postojanje povezanosti između akutnog odbacivanja i T-alela, samo u afričkoj populaciji (23). Polimorfizam rs5742909 je ispitivan u studiji koju su sproveli Eting (Oetting) i saradnici (24), pri čemu nisu detektovali povezanost ovog polimorfizma sa akutnim odbacivanjem bubrega.…”

Section: Diskusijaunclassified

Evaluation of the - 318C/T (RS5742909) CTLA4 gene polymorphism influence on kidney function after transplantation

Veljančić¹,

Perović²

2021

Medicinski podmladak

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Introduction: The protein CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) is a molecule that plays a significant role in maintaining immunological homeostasis. Recent studies demonstrated an unequivocal proof that CTLA-4 has an inhibitory effect on immune response. This gene has been identified with several single nucleotide polymorphisms which could change gene activity, consequently leading to structural protein change. This genetic variability is associated with acute rejection and delayed graft function as important indicators of kidney transplantation success. Aim: The aim of this study was to evaluate the potential association of CTLA4 (rs5742909) polymorphisms with acute rejection and delayed graft function in patients with kidney transplant. Material and methods: A total of 151 patients were included in this cross-sectional cohort study. Real-time polymerase chain reaction was used to determine the genotype which was then evaluated in relation to acute rejection and delayed graft function. Statistical significance was analyzed by Pearson's Chi-square and Fisher's exact test. Results: The most frequent genotype among 151 patient was CC (80.8%), then CT (17.9%) and TT (1.3%). The frequency of C allele is 89.7% whereas the frequency of T allele is 10.3%. There was no statistically significant difference in CTLA4 genotype and allele distribution nor their linkage to acute rejection and delayed graft function. The evaluation of C or T allele carriers showed no statistically significant difference with respect to previously mentioned posttransplant complications. Conclusion: In this study, no statistically significant association between -318C/T (rs5742909) CTLA4 polymorphism and AR/DGF was found.

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Relationship between cytotoxic T‐lymphocyte antigen 4 ‐318C/T (rs5742909) gene polymorphism and the risk of acute rejection in renal transplantation

Cited by 5 publications

References 22 publications

CTLA-4 rs231775 and risk of acute renal graft rejection: an updated meta-analysis with trial sequential analysis

CTLA-4 rs231775 and risk of acute renal graft rejection: an updated meta-analysis with trial sequential analysis

The Role of CTLA4 and Its Polymorphisms in Solid Organ and Haematopoietic Stem Cell Transplantation

Evaluation of the - 318C/T (RS5742909) CTLA4 gene polymorphism influence on kidney function after transplantation

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