Polymorphisms in cytotoxic T lymphocyte associated antigen-4 influence the rate of acute rejection after renal transplantation in 167 Chinese recipients

Gao, Junwei; Guo, Yuxin; Yu, Fan; Qiu, Jianxin; Bao, Erdun; Liu, Yong; Yan, Qin; Zhang, Fang

doi:10.1016/j.trim.2012.02.005

Cited by 25 publications

(30 citation statements)

References 24 publications

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“…It has been speculated that rs4553808 (−1661) AA plays a protective role in the autoimmune disease and that the genotype GG as the risk factor for SLE. Likewise, rs733618 (−1772) TT was found to be associated with the risk of AR following renal transplantation in our previous study [17]. Our study revealed that the frequency of the rs4553808 GG genotype was higher in the viral infection cohort than in the non-viral infection group ( p = 0.001).…”

Section: Discussionsupporting

confidence: 64%

“…The percentage of AR recipient with bacterial infection (32/61, 52.46%) was higher than that of non-AR recipients (95/243, 39.09%), although this difference only approached significance ( p = 0.058). In our previous study [17], a correlation between CTLA4 SNPs and AR was observed. That data was not sufficient to determine whether AR is associated with a higher risk of infection, but a multivariate analysis published by Mourad et al [33] this year showed that acute rejection was a risk factor for infectious complications after renal transplantation.…”

Section: Discussionmentioning

confidence: 71%

“…The loci rs733618 (−1772) and rs4553808(−1661), rs3087243 (+6230) have been studied in relation to type 1 diabetes, systemic lupus erythematosus (SLE), cancer, organ transplantation and other diseases [17], [26]–[30]. It has been speculated that rs4553808 (−1661) AA plays a protective role in the autoimmune disease and that the genotype GG as the risk factor for SLE.…”

Section: Discussionmentioning

confidence: 99%

“…The rs3087243 (+6230G/A) SNP is located within the 3′ untranslated region of the CTLA-4 gene and was found to be associated with susceptibility to autoimmune diseases [11]. Furthermore, the SNPs within the CTLA4 gene, such as −1772T/C (rs733618), +49A/G (rs231775) and +6230 G/A (rs3087243), play an influential role in graft rejection and the long-term clinical outcome of organ transplantation [12]–[17].…”

Section: Introductionmentioning

confidence: 99%

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CTLA4 Gene Polymorphisms Influence the Incidence of Infection after Renal Transplantation in Chinese Recipients

Guo

Wei

et al. 2013

PLoS ONE

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BackgroundImmunosuppressive therapy is usually administered following renal transplantation to protect the graft from rejection. However, this often causes complications such as infections to occur. Single nucleotide polymorphisms (SNPs) within the CTLA4 gene, such as −1772T/C (rs733618), +49A/G (rs231775) and +6230 G/A (rs3087243), can affect graft rejection and the long-term clinical outcome of organ transplantation. The role of CTLA4 SNPs in T cell-mediated immunity in renal transplantation and association with infection after transplantation is unknown.MethodsIn this study, the risk of infection according to CTLA4 SNPs was investigated in 304 patients who received kidney graft transplants between 2008 and 2012.ResultsThe frequency of the rs4553808 GG genotype was significantly higher in recipients with viral infection (14.89%) than in those without infections (3.50%) (Bonferroni-adjusted p = 0.005). A significant difference (p = 0.001) in patients with the rs4553808 GG genotype from those with the AA+AG genotypes was found in the viral cohort using the log-rank test. A significant association was found between the rs4553808 genotype and onset of viral infection in transplant recipients (p = 0.001). The frequencies of the CGTAG and CGCAG haplotypes were significantly higher in the viral infection group (9.6% and 5.3%) than in the non-viral infection group (3.8% and 1.4%) (p = 0.0149 and p = 0.0111). No association between any CTLA4 SNP and bacterial infection was found. Multivariate analyses revealed that one risk factor, the use of antibody induction therapy (p = 0.007), was associated with bacterial infection, and two risk factors, antibody use (p = 0.015) and recipient rs4553808 genotype (p = 0.001), were associated with viral infection.ConclusionsThe rs4553808 GG genotype may be a risk factor for viral infection in kidney transplantation. The CTLA4 haplotypes CGTAG and CGCAG were partially associated with the development of viral infection in Chinese kidney transplant recipients.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

CTLA4 Gene Polymorphisms Influence the Incidence of Infection after Renal Transplantation in Chinese Recipients

Guo

Wei

et al. 2013

PLoS ONE

Self Cite

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“…The gene behaves as a critical negative regulator of the T cell-mediated immune response that can inhibit T Helper (TH) 1 and TH2 cytokine production and cell cycle progression in antigen presenting cells (APC) [29] . Numerous studies have shown the association of CTLA-4 polymorphisms with allograft rejection, endstage renal disease, delayed graft function and infection after renal transplantation [29][30][31][32] , and the expression pattern of the protein encoded by CTLA4 was found to be altered by the polymorphisms rs4553808 (-1661A/G) in the CTLA4 gene promoter [33] . It is reported that a carry of G allele variation will increase CTLA4 mRNA level and expression, thereby promoting consensus sequence in the regulatory region of the CTLA4 promoter in humans [26,34] .…”

Section: Discussionmentioning

confidence: 99%

IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients

Liu

Zhang

et al. 2017

Acta Pharmacol Sin

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The highly variable pharmacokinetics and narrow therapeutic window of tacrolimus (TAC) has hampered its clinical use. Genetic polymorphisms may contribute to the variable response, but the evidence is not compelling, and the explanation is unclear. In this study we attempted to find previously unknown genetic factors that may influence the TAC dose requirements. The association of 105 pathway-related single nucleotide polymorphisms (SNPs) with TAC dose-adjusted concentrations (C0/D) was examined at 7, 30 and 90 d post-operation in 382 Chinese kidney transplant recipients. In CYP3A5 non-expressers, the patients carrying the IL-3 rs181781 AA genotype showed a significantly higher TAC logC0/D than those with the AG genotype at 30 and 90 d post-operation (AA vs AG, 2.21±0.06 vs 2.01±0.03, P=0.004; and 2.17±0.06 vs 2.03±0.03, P=0.033, respectively), and than those with the GG genotype at 30 d (AA vs GG, 2.21±0.06 vs 2.04±0.03, P=0.011). At 30 d, the TAC logC0/D in the grouped AG+GG genotypes of CTLA4 rs4553808 was significantly lower than that in the AA genotype (P=0.041) in CYP3A5 expressers, but it was higher (P=0.008) in the non-expressers. We further validated the influence of CYP3A5 rs776746, CYP3A4 rs2242480 and rs4646437 on the TAC C0/D; other candidate SNPs were not associated with the differences in TAC C0/D. In conclusion, genetic polymorphisms in the immune genes IL-3 rs181781 and CTLA4 rs4553808 may influence the TAC C0/D. They may, together with CYP3A5 rs776746, CYP3A4 rs2242480 and rs4646437, contribute to the variation in TAC dose requirements. When conducting individualized therapy with tacrolimus, these genetic factors should be taken into account.

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Influence of cytotoxic T lymphocyte antigen 4 genetic variants on acute rejection in kidney transplant patients: precision medicine perspective

Taleb

Afshari

Samzadeh

et al. 2021

J Diabetes Metab Disord

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Background The most effective and common treatment for end-stage renal disease is kidney transplantation. The personalized approach to kidney transplantation, which utilizes precision medicine principles, determines distinctive genomics characteristics of candidates/recipients that must be taken into account. Cytotoxic T lymphocyte associated protein 4 (CTLA4) may be a suitable candidate gene for studying allograft rejection. The aim of this study was to understand whether we can consider two common variants of the CTLA4 gene as a risk factor of transplant rejection in a group of Iranian population. Methods Totally, 169 kidney transplant recipients, including acute rejections (N=39) and non-rejection (N=130) groups who underwent transplantation were included in this study. The genotyping of rs5742909 (−318C/T) and rs231775 (+49A/G) variants of the CTLA4 gene were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. ResultsThe AG genotype frequency of rs231775 variant was the same in both patients with and without a history of rejection while, none of those groups had homozygote genotype. In rs5742909, both CT and TT frequencies of patients with rejected transplant were lower than patients with a normal outcome. ConclusionsThe results of the presented study suggest that rs231775 and rs5742909 of CTLA4 genetic variants are not linked to acute rejection who underwent kidney transplantation. So, these variants cannot be considered as risk factors of acute allograft rejection in a group of Iranian renal transplantation recipients. However, the transplantation precision medicine may be an important area for the improvement of patients outcome as the precision medicine has already entered clinical practice in kidney transplantation.

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Polymorphisms in cytotoxic T lymphocyte associated antigen-4 influence the rate of acute rejection after renal transplantation in 167 Chinese recipients

Cited by 25 publications

References 24 publications

CTLA4 Gene Polymorphisms Influence the Incidence of Infection after Renal Transplantation in Chinese Recipients

CTLA4 Gene Polymorphisms Influence the Incidence of Infection after Renal Transplantation in Chinese Recipients

IL-3 and CTLA4 gene polymorphisms may influence the tacrolimus dose requirement in Chinese kidney transplant recipients

Influence of cytotoxic T lymphocyte antigen 4 genetic variants on acute rejection in kidney transplant patients: precision medicine perspective

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