Cytokine Gene Polymorphism Profiles in Kidney Transplant Patients - Association of +1188A/C RS3212227 SNP in the IL12B Gene Prevents Delayed Graft Function

Perović, Vladimir; Marković, Miloš; Kravljača, Milica; Milošević, Emina; Djoric, Milica; Pravica, Vera; Naumovic, Radomir

doi:10.1016/j.arcmed.2018.04.015

Cited by 5 publications

(8 citation statements)

References 43 publications

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“…In fact, observed complications and interindividual differences cannot be fully explained by classical risk factors alone and seem inter alia to depend on genetic variations [ 6 , 13 , 14 ]. Regarding genetic variations, several candidate genes such as those for cytochrome P450 and interleukins have been implicated [ 15 , 16 ]. Aquaporins (AQPs) are related to immune cell and kidney function [ 17 ] and thus, might be of special interest.…”

Section: Introductionmentioning

confidence: 99%

The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration

Rump

Rahmel

Rustige

et al. 2020

Cells

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Major complications after kidney transplantation are graft rejection and cytomegalovirus (CMV) infection, which are related to T-cell function, which depends on aquaporin 3 (AQP3) expression. The impact of the AQP3 A(−1431)G promoter polymorphism in kidney transplant recipients was unelucidated and we explored the effect of AQP3 polymorphism on immune cell function and its association with graft rejection and CMV infection in 237 adult patients within 12 months after transplantation. AQP3 promoter polymorphism was molecular and functional characterized. Kaplan–Meier plots evaluated the relationship between genotypes and the incidence of CMV infection and graft rejection. AQP3 A(−1431)G A-allele was associated with enhanced immune cell migration and AQP3 expression in T-cells. The incidences of rejection were 45.4% for the A-allele and 27.1% for G-allele carriers (p = 0.005) and the A-allele was a strong risk factor (hazard ratio (HR): 1.95; 95% CI: 1.216 to 3.127; p = 0.006). The incidences for CMV infection were 21% for A-allele and 35% for G-allele carriers (p = 0.013) and G-allele was an independent risk factor (p = 0.023), with a doubled risk for CMV infection (HR: 1.9; 95% CI: 1.154 to 3.128; p = 0.012). Hence, A-allele confers more resistance against CMV infection, but susceptibility to graft rejection mediated by T-cells. Thus, AQP3-genotype adapted management of immunosuppression and antiviral prophylaxis after kidney transplantation seems prudent.

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Section: Introductionmentioning

confidence: 99%

The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration

Rump

Rahmel

Rustige

et al. 2020

Cells

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“…Conversely, the IFNG 874TT genotype was Rosario Dominguez Crespo Hirata, Fabiana Dalla Vecchia Genvigir, Thiago Dominguez Crespo Hirata, Alvaro Cerda, Mario Hiroyuki Hirata associated with reduced risk of AR (OR: 0.40, 95%CI: 0.19-0.85, p<0.05) and high graft survival time in adult kidney recipients on long-term treatment (Vu et al, 2014a) (Table III). Other studies did not find an influence of the IFNG 874T>A on AR in small (Gendzekhadze et al, 2006;Azarpira et al, 2009;Gaafar et al, 2014;Perovic et al, 2018) and larger (Singh et al, 2009;Dhaouadi et al, 2013;Vu et al, 2014b) cohorts of adult kidney recipients on MMF treatment (Table IV).…”

Section: Ifngmentioning

confidence: 89%

“…Other studies reported no impact of the TNF -308G>A on AR in adult patients from different cohorts on short-term (Azarpira et al, 2009;Cilião et al, 2017;Hu et al, 2020) or long-term on MMF therapy (Weimer et al, 2003;Dmitrienko et al, 2005). (Gendzekhadze et al, 2006;Dhaouadi et al, 2013;Gaafar et al, 2014;Perovic et al, 2018) (Table IV). Interestingly, the TNF*H/TGFB1*H/IL10*H haplotype, which includes the TNF -308A allele (H*), was associated with increased risk of AR (OR: 15.75.…”

Section: Tnfmentioning

confidence: 96%

“…TNF -308G>A was associated with reduced risk of chronic rejection (-308A allele, OR: 0.1, 95%CI: 0.005-1.64, p<0.05) in a small cohort of adult kidney recipients (Gendzekhadze et al, 2006) (Table III). On the other hand, this variant did not increase the risk of chronic graft nephropathy (Satoh et al, 2007) chronic rejection (Dhaouadi et al, 2013), DGF or graft function (Perovic et al, 2018), and graft failure or patient death (Dmitrienko et al, 2005) in adult kidney recipients (Table IV). A recent study found TNF -308G allele carriers had low eGFR, but not with IL-6 and IL-10 plasma levels, in adult patients on long-term MMF therapy (Alves et al, 2020).…”

Section: Tnfmentioning

confidence: 97%

“…The IL12B 1188A>C was associated with reduced risk of DGF (AA genotype, OR: 0.45, 95%CI: 0.21-0.96, p<0.05) (Table III), but this variant had no impact on AR or graft function in adult kidney recipients on MMF treatment (Perovic et al, 2018). Earlier studies, also reported a lack of association of the IL12B 1188A>C with AR, DGF, graft survival, or chronic graft nephropathy (Satoh et al, 2007;Hoffmann et al, 2009) (Table IV).…”

Section: Genes Related To Pro-inflammatory Cytokinesmentioning

confidence: 99%

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Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes

Hirata

Genvigir

Hirata

et al. 2022

Braz. J. Pharm. Sci.

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Mycophenolic acid (MPA) inhibits IMPDH, involved in the guanosine nucleotides synthesis, and prevents DNA replication in immune cells. The repression of cell and humoral immunity by MPA induces allograft tolerance preventing acute rejection in solid organ transplantation. MPA is an effective and safe drug, but genetic and non-genetic factors have been implicated in the interindividual variability of drug response. Several studies have shown the impact of variants of pharmacokinetics or pharmacodynamics-related genes on MPA response in kidney transplantation. This review explored further the influence of genes involved in the immune response on clinical outcomes of kidney recipients on short-or long-term MPA treatment. Variants in genes related to T cell activation (CD28, CTL4, ICOS, PDPC1), pro-inflammatory cytokines (IL2, IL6, IL12A, IL12B, TNF, IFNG), immunomodulatory cytokines (IL4, IL10, TGFB1), and innate immune response (CD14, TLR2, TLR4) were shown to be associated with increased risk of acute rejection, graft function or survival, chronic graft nephropathy, viral infections or MPA-induced myelotoxicity. Some of the significant pharmacogenetic associations were confirmed by meta-analyses of kidney transplantation. These findings are suggestive that variants in immune response-related genes contribute to the variability of MPA response, and have potential application as biomarkers of acute rejection in kidney transplantation.

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TNF, IL-6, and IL-10 cytokines levels and their polymorphisms in renal function and time after transplantation

et al. 2020

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Cytokine Gene Polymorphism Profiles in Kidney Transplant Patients - Association of +1188A/C RS3212227 SNP in the IL12B Gene Prevents Delayed Graft Function

Cited by 5 publications

References 43 publications

The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration

The Aquaporin 3 Promoter Polymorphism −1431 A/G is Associated with Acute Graft Rejection and Cytomegalovirus Infection in Kidney Recipients Due to Altered Immune Cell Migration

Pharmacogenomics of mycophenolic acid in kidney transplantation: Contribution of immune response-related genes

TNF, IL-6, and IL-10 cytokines levels and their polymorphisms in renal function and time after transplantation

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