Impact of TBX21, GATA3, and FOXP3 gene polymorphisms on acute cellular rejection after liver transplantation

Thude, Hansjörg; Tiede, Petra; Sterneck, Martina; Nashan, Björn; Koch, Martina

doi:10.1111/tan.13458

Cited by 6 publications

(7 citation statements)

References 33 publications

(76 reference statements)

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“…Thus, in the case of TBX21 -1993C allele of the SNP rs4794067 there is association with the predominance of the Th17 cell activity. TBX21 SNP rs4794067 was already associated with reumathoid artritis, asthma or type 1 diabetes mellitus ( Sasaki et al, 2004 ; Chae et al, 2009 ), but no association was found with acute cellular LT rejection ( Thude et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Host and immunosuppression-related factors influencing fibrosis occurrence post liver transplantation

Iacob

Iacob²,

Manea³

et al. 2022

Front. Pharmacol.

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Post liver transplantation (LT) fibrosis has a negative impact on graft function. Cytokine production in the host immune response after LT may contribute to the variable CYP3A-dependent immunosuppressive drug disposition, with subsequent impact on liver fibrogenesis, together with host-related factors. We aimed to investigate whether the cytochrome P4503A5*3 (CYP3A5*3) or TBX21 genotypes impact post-LT liver fibrogenesis. Furthermore, the impact of immunosuppressants on cellular apoptosis has been evaluated using human hepatocytes harvested from cirrhotic explanted livers. We have enrolled 98 LT recipients that were followed for occurrence of liver fibrosis for at least 12 months. There was a statistically significant higher trough level of TAC in patients with homozygous CC-TBX21 genotype (7.83 ± 2.84 ng/ml) vs. 5.66 ± 2.16 ng/ml in patients without this genotype (p = 0.009). The following variables were identified as risk factors for fibrosis ≥2: donor age (p = 0.02), neutrophil to lymphocyte ratio (p = 0.04) and TBX21 genotype CC (p = 0.009). In the cell culture model cytometry analysis has indicated the lowest apoptotic cells percentage in human cirrhotic hepatocytes cultures treated with mycophenolate mofetil (MMF) (5%) and TAC + MMF (2%) whereas the highest apoptosis percentage was registered for the TAC alone (11%). The gene expression results are concordant to cytometry study results, indicating the lowest apoptotic effect for MMF and MMF + TAC immunosuppressive regimens. The allele 1993C of the SNP rs4794067 may predispose to the development of late significant fibrosis of the liver graft. MMF-based regimens have a favourable anti-apoptotic profile in vitro, supporting its use in case of LT recipients at high risk for liver graft fibrosis.

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Section: Discussionmentioning

confidence: 99%

Host and immunosuppression-related factors influencing fibrosis occurrence post liver transplantation

Iacob

Iacob²,

Manea³

et al. 2022

Front. Pharmacol.

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“…Besides vitiligo ,FOXP3 rs3761548C< A was found to be associated with other autoimmune disorders like multiple sclerosis 42 , systemic lupus erythematosus 43 , Graves' Disease 44 , acute cellular rejection after liver transplantation 45 46 and idiopathic recurrent miscarriages 47 .…”

Section: Discussionmentioning

confidence: 99%

Association Between Foxp3 (Rs3761548) Promoter Polymorphism With Vitiligo Patients, Their Clinical Data and Response to Phototherapy: A Study From Egypt

Abdel‐Salam

Zohdy²,

Wassefy³

et al. 2022

Bulletin of Pharmaceutical Sciences. Assiut

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Background:The rs3761548 polymorphism (3279 C> A) of the FOXP3 gene is associated with several autoimmune disorders. Its role in vitiligo has not been well studied.We sought to investigate whether rs3761548 polymorphism is associated with vitiligo in Egyptian subjects. Methods:Case-control study where genomic DNA was isolated from blood samples of 100 patients and 100 control subjects and genotyping was done by allele-specific primers. Given that FOXP3 is an X-linked marker, data analysis was done for the entire cohort and then stratified based on the gender. Results:The genotype frequencies differed significantly from patients to control subjects showing that AC genotype was significantly higher in the patient group than control subjects (risky genotype ) despite of the protective nature of CC genotype which observed in our study. According to the alleles , the A allele was higher in the patient than in the control group .Insignificant results were reported according to the association between FOXP3 (rs3761548) promoter polymorphism and clinical data of patients and their response to phototherapy.Conclusions: The rs3761548 of FOXP3 gene may be associated with susceptibility to vitiligo because of altered expression.Both the A allele and AC genotype were significantly associated with vitiligo .

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“…On the other hand, the CC genotype (70%) and the C allele (72.5%) were significantly more predominant in healthy volunteers as compared to transplant recipients with ACR (23.3% and 28.3% respectively). Thude et al, 25 reported that the frequency of the genotype −3279 AA was 41% and 25% in transplant recipients with and without ACR respectively. Similarly, the −3279 A allele was more frequent in the transplant recipients with (50%) than in those without ACR (35%).…”

Section: Discussionmentioning

confidence: 99%

Role of circulating CD4+CD25+FOXP-3+T-regulatory cells and FOXP-3 rs3761548 gene polymorphism in acute liver allograft rejection

Ghoneim

Ghonaim

Makled

et al. 2020

Egyptian Journal of Medical Microbiology

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Background: FOXP3 gene, is a major regulator of T-regulatory (Treg) cells that have a critical role in immune responses to alloantigens and acute cellular rejection (ACR) after liver transplantation (LT). Objectives: To investigate the role of FOXP-3 rs3761548 gene polymorphism on ACR after LT and to determine the relation between the circulating CD4 + CD25 + FOXP-3 + Treg cells, and infection on the severity of ACR.Methodology: Blood samples were obtained from 60 allograft liver recipients and 20 healthy volunteers. FOXP-3 (rs3761548) polymorphism was studied using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Flowcytometry was used to enumerate circulating CD4 + CD25 + FOXP-3 + Treg cells in peripheral blood of liver transplant recipients. Results: Bacterial and candida infections were more significantly detected in liver transplant recipients with ACR. A significant predominance of the AA genotype and the A allele of FOXP3 gene (rs3761548) was found in liver transplant recipients with compared to those without ACR. Highly significant reduction in percentage and count of CD4 + and Treg cells were demonstrated in the liver transplant recipients with ACR. A significant negative correlation was detected between degree of ACR and percentage and count of Treg cells. Conclusion: Genetic polymorphism of FOXP-3 (rs3761548) and decreased percentage and count of Treg cells were associated with ACR. Carriers of the AA genotype and the A allele were more liable to severe degree of ACR after LT.

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Impact of TBX21, GATA3, and FOXP3 gene polymorphisms on acute cellular rejection after liver transplantation

Cited by 6 publications

References 33 publications

Host and immunosuppression-related factors influencing fibrosis occurrence post liver transplantation

Host and immunosuppression-related factors influencing fibrosis occurrence post liver transplantation

Association Between Foxp3 (Rs3761548) Promoter Polymorphism With Vitiligo Patients, Their Clinical Data and Response to Phototherapy: A Study From Egypt

Role of circulating CD4+CD25+FOXP-3+T-regulatory cells and FOXP-3 rs3761548 gene polymorphism in acute liver allograft rejection

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