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Published in: World Journal of Urology 1/2018

Open Access 01-01-2018 | Original Article

Polymorphisms of nucleotide factor of activated T cells cytoplasmic 2 and 4 and the risk of acute rejection following kidney transplantation

Authors: Zijie Wang, Haiwei Yang, Shuhui Si, Zhijian Han, Jun Tao, Hao Chen, Yuqiu Ge, Miao Guo, Ke Wang, Ruoyun Tan, Ji-Fu Wei, Min Gu

Published in: World Journal of Urology | Issue 1/2018

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Abstract

Background

Acute rejection (AR) is a common complication of kidney transplantation. Nuclear factors of activated T cells (NFATs) are transcription factors involved in the activation of T lymphocytes, but their association with AR is unclear.

Methods

This retrospective, case–control study included 200 renal transplant recipients who were divided into the AR group (n = 69) and stable group (n = 131). Their blood samples were collected, and DNA was extracted from the whole blood. High-throughput next-generation sequencing was used to identify single nucleotide polymorphisms (SNPs) of the NFATC2 and NFATC4 genes. The correlation of these SNPs with AR was determined by logistic analysis.

Results

Seventy-one SNPs of the NFATC2 and NFATC4 genes were identified by the sequencing and Hardy–Weinberg equilibrium analyses. After adjusting for age, gender and immunosuppressive protocols, 27 SNPs were correlated with AR, of which the SNP rs2426295 of the NFATC2 gene showed a significant correlation with AR in the HET model (AA vs. AC: OR = 0.43, 95% CI = 0.19–0.98, P = 0.045), but no significant NFATC4 SNPs were identified.

Conclusions

Our study shows that the rs2426295 variant of the NFATC2 gene is significantly associated with the occurrence of AR following kidney transplantation. And patients with AA genotypes in rs2426295 are inclined to suffer from AR pathogenesis.
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Literature
2.
go back to reference Matas AJ, Hays RE, Ibrahim HN (2017) Long-term non-end-stage renal disease risks after living kidney donation. Am J Transplant 17(4):893–900CrossRefPubMed Matas AJ, Hays RE, Ibrahim HN (2017) Long-term non-end-stage renal disease risks after living kidney donation. Am J Transplant 17(4):893–900CrossRefPubMed
3.
go back to reference Williams WW, Taheri D, Tolkoff-Rubin N, Colvin RB (2012) Clinical role of the renal transplant biopsy. Nature Rev Nephrol 8(2):110–121CrossRef Williams WW, Taheri D, Tolkoff-Rubin N, Colvin RB (2012) Clinical role of the renal transplant biopsy. Nature Rev Nephrol 8(2):110–121CrossRef
4.
go back to reference von Toerne C, Schmidt C, Adams J, Kiss E, Bedke J, Porubsky S et al (2009) Wnt pathway regulation in chronic renal allograft damage. Am J Transplant 9(10):2223–2239CrossRef von Toerne C, Schmidt C, Adams J, Kiss E, Bedke J, Porubsky S et al (2009) Wnt pathway regulation in chronic renal allograft damage. Am J Transplant 9(10):2223–2239CrossRef
5.
go back to reference Lee YH, Martin-Orozco N, Zheng P, Li J, Zhang P, Tan H et al (2017) Inhibition of the B7–H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function. Cell Res 27(8):1034–1045CrossRefPubMed Lee YH, Martin-Orozco N, Zheng P, Li J, Zhang P, Tan H et al (2017) Inhibition of the B7–H3 immune checkpoint limits tumor growth by enhancing cytotoxic lymphocyte function. Cell Res 27(8):1034–1045CrossRefPubMed
6.
go back to reference Mantuano E, Azmoon P, Brifault C, Banki MA, Gilder AS, Campana WM et al (2017) Tissue-type plasminogen activator regulates macrophage activation and innate immunity. Blood 130(11):1364–1374CrossRefPubMed Mantuano E, Azmoon P, Brifault C, Banki MA, Gilder AS, Campana WM et al (2017) Tissue-type plasminogen activator regulates macrophage activation and innate immunity. Blood 130(11):1364–1374CrossRefPubMed
7.
go back to reference Crabtree GR, Olson EN (2002) NFAT signaling: choreographing the social lives of cells. Cell 109:S67–S79CrossRefPubMed Crabtree GR, Olson EN (2002) NFAT signaling: choreographing the social lives of cells. Cell 109:S67–S79CrossRefPubMed
8.
go back to reference Lawrence MC, Borenstein-Auerbach N, McGlynn K, Kunnathodi F, Shahbazov R, Syed I et al (2015) NFAT targets signaling molecules to gene promoters in pancreatic beta-cells. Mol Endocrinol 29(2):274–288CrossRefPubMed Lawrence MC, Borenstein-Auerbach N, McGlynn K, Kunnathodi F, Shahbazov R, Syed I et al (2015) NFAT targets signaling molecules to gene promoters in pancreatic beta-cells. Mol Endocrinol 29(2):274–288CrossRefPubMed
9.
go back to reference McCaffrey PG, Luo C, Kerppola TK, Jain J, Badalian TM, Ho AM et al (1993) Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science 262(5134):750–754CrossRefPubMed McCaffrey PG, Luo C, Kerppola TK, Jain J, Badalian TM, Ho AM et al (1993) Isolation of the cyclosporin-sensitive T cell transcription factor NFATp. Science 262(5134):750–754CrossRefPubMed
10.
go back to reference Northrop JP, Ho SN, Chen L, Thomas DJ, Timmerman LA, Nolan GP et al (1994) NF-AT components define a family of transcription factors targeted in T-cell activation. Nature 369(6480):497–502CrossRefPubMed Northrop JP, Ho SN, Chen L, Thomas DJ, Timmerman LA, Nolan GP et al (1994) NF-AT components define a family of transcription factors targeted in T-cell activation. Nature 369(6480):497–502CrossRefPubMed
11.
go back to reference Rooney JW, Hoey T, Glimcher LH (1995) Coordinate and cooperative roles for NF-AT and AP-1 in the regulation of the murine IL-4 gene. Immunity 2(5):473–483CrossRefPubMed Rooney JW, Hoey T, Glimcher LH (1995) Coordinate and cooperative roles for NF-AT and AP-1 in the regulation of the murine IL-4 gene. Immunity 2(5):473–483CrossRefPubMed
12.
go back to reference Pan S, Tsuruta R, Masuda ES, Imamura R, Bazan F, Arai K et al (2000) NFATz: a novel rel similarity domain containing protein. Biochem Biophys Res Commun 272(3):765–776CrossRefPubMed Pan S, Tsuruta R, Masuda ES, Imamura R, Bazan F, Arai K et al (2000) NFATz: a novel rel similarity domain containing protein. Biochem Biophys Res Commun 272(3):765–776CrossRefPubMed
13.
go back to reference Masuda ES, Naito Y, Tokumitsu H, Campbell D, Saito F, Hannum C et al (1995) NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus. Mol Cell Biol 15(5):2697–2706CrossRefPubMedPubMedCentral Masuda ES, Naito Y, Tokumitsu H, Campbell D, Saito F, Hannum C et al (1995) NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus. Mol Cell Biol 15(5):2697–2706CrossRefPubMedPubMedCentral
14.
go back to reference Bremer S, Vethe NT, Skauby M, Kasbo M, Johansson ED, Midtvedt K, et al (2017) NFAT-regulated cytokine gene expression during tacrolimus therapy early after renal transplantation. Br J Clin Pharmacol 83(11):2494–2502CrossRefPubMed Bremer S, Vethe NT, Skauby M, Kasbo M, Johansson ED, Midtvedt K, et al (2017) NFAT-regulated cytokine gene expression during tacrolimus therapy early after renal transplantation. Br J Clin Pharmacol 83(11):2494–2502CrossRefPubMed
15.
go back to reference Singh NK, Janjanam J, Rao GN (2017) p115 RhoGEF activates the Rac1 GTPase signaling cascade in MCP1-induced vascular smooth muscle cell migration and proliferation. J Biol Chem 292(34):14080–14091CrossRefPubMed Singh NK, Janjanam J, Rao GN (2017) p115 RhoGEF activates the Rac1 GTPase signaling cascade in MCP1-induced vascular smooth muscle cell migration and proliferation. J Biol Chem 292(34):14080–14091CrossRefPubMed
16.
go back to reference Vihma H, Timmusk T (2017) Sumoylation regulates the transcriptional activity of different human NFAT isoforms in neurons. Neurosci Lett 653:302–307CrossRefPubMed Vihma H, Timmusk T (2017) Sumoylation regulates the transcriptional activity of different human NFAT isoforms in neurons. Neurosci Lett 653:302–307CrossRefPubMed
17.
go back to reference Cui C, Merritt R, Fu L, Pan Z (2017) Targeting calcium signaling in cancer therapy. Acta Pharm Sin B 7(1):3–17CrossRefPubMed Cui C, Merritt R, Fu L, Pan Z (2017) Targeting calcium signaling in cancer therapy. Acta Pharm Sin B 7(1):3–17CrossRefPubMed
18.
go back to reference Won HY, Hwang ES (2016) Transcriptional modulation of regulatory T cell development by novel regulators NR4As. Arch Pharmacal Res 39(11):1530–1536CrossRef Won HY, Hwang ES (2016) Transcriptional modulation of regulatory T cell development by novel regulators NR4As. Arch Pharmacal Res 39(11):1530–1536CrossRef
19.
go back to reference Mognol GP, Carneiro FR, Robbs BK, Faget DV, Viola JP (2016) Cell cycle and apoptosis regulation by NFAT transcription factors: new roles for an old player. Cell Death Dis 7:e2199CrossRefPubMedPubMedCentral Mognol GP, Carneiro FR, Robbs BK, Faget DV, Viola JP (2016) Cell cycle and apoptosis regulation by NFAT transcription factors: new roles for an old player. Cell Death Dis 7:e2199CrossRefPubMedPubMedCentral
20.
go back to reference Aramburu J, Azzoni L, Rao A, Perussia B (1995) Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding. J Exp Med 182(3):801–810CrossRefPubMed Aramburu J, Azzoni L, Rao A, Perussia B (1995) Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding. J Exp Med 182(3):801–810CrossRefPubMed
21.
go back to reference Rao A, Luo C, Hogan PG (1997) Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 15:707–747CrossRefPubMed Rao A, Luo C, Hogan PG (1997) Transcription factors of the NFAT family: regulation and function. Annu Rev Immunol 15:707–747CrossRefPubMed
22.
go back to reference Xanthoudakis S, Viola JP, Shaw KT, Luo C, Wallace JD, Bozza PT et al (1996) An enhanced immune response in mice lacking the transcription factor NFAT1. Science 272(5263):892–895CrossRefPubMed Xanthoudakis S, Viola JP, Shaw KT, Luo C, Wallace JD, Bozza PT et al (1996) An enhanced immune response in mice lacking the transcription factor NFAT1. Science 272(5263):892–895CrossRefPubMed
23.
go back to reference Karwot R, Ubel C, Bopp T, Schmitt E, Finotto S (2012) Increased immunosuppressive function of CD4(+) CD25(+) Foxp3(+) GITR+ T regulatory cells from NFATc2((−/−)) mice controls allergen-induced experimental asthma. Immunobiology 217(9):905–911CrossRefPubMed Karwot R, Ubel C, Bopp T, Schmitt E, Finotto S (2012) Increased immunosuppressive function of CD4(+) CD25(+) Foxp3(+) GITR+ T regulatory cells from NFATc2((−/−)) mice controls allergen-induced experimental asthma. Immunobiology 217(9):905–911CrossRefPubMed
24.
25.
go back to reference Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M et al (2008) Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 8(4):753–760CrossRefPubMed Solez K, Colvin RB, Racusen LC, Haas M, Sis B, Mengel M et al (2008) Banff 07 classification of renal allograft pathology: updates and future directions. Am J Transplant 8(4):753–760CrossRefPubMed
26.
go back to reference Fernandez CA, Smith C, Yang W, Mullighan CG, Qu C, Larsen E et al (2015) Genome-wide analysis links NFATC2 with asparaginase hypersensitivity. Blood 126(1):69–75CrossRefPubMedPubMedCentral Fernandez CA, Smith C, Yang W, Mullighan CG, Qu C, Larsen E et al (2015) Genome-wide analysis links NFATC2 with asparaginase hypersensitivity. Blood 126(1):69–75CrossRefPubMedPubMedCentral
27.
go back to reference Petra H, Eva H, Irena B, Petra H, Ondrej V (2013) Molecular profiling of acute and chronic rejections of renal allografts. Clin Dev Immunol 2013:509259CrossRefPubMedPubMedCentral Petra H, Eva H, Irena B, Petra H, Ondrej V (2013) Molecular profiling of acute and chronic rejections of renal allografts. Clin Dev Immunol 2013:509259CrossRefPubMedPubMedCentral
28.
go back to reference Chen Y, Sampaio MS, Yang JW, Min D, Hutchinson IV (2012) Genetic polymorphisms of the transcription factor NFATc4 and development of new-onset diabetes after transplantation in Hispanic kidney transplant recipients. Transplantation 93(3):325–330CrossRefPubMed Chen Y, Sampaio MS, Yang JW, Min D, Hutchinson IV (2012) Genetic polymorphisms of the transcription factor NFATc4 and development of new-onset diabetes after transplantation in Hispanic kidney transplant recipients. Transplantation 93(3):325–330CrossRefPubMed
Metadata
Title
Polymorphisms of nucleotide factor of activated T cells cytoplasmic 2 and 4 and the risk of acute rejection following kidney transplantation
Authors
Zijie Wang
Haiwei Yang
Shuhui Si
Zhijian Han
Jun Tao
Hao Chen
Yuqiu Ge
Miao Guo
Ke Wang
Ruoyun Tan
Ji-Fu Wei
Min Gu
Publication date
01-01-2018
Publisher
Springer Berlin Heidelberg
Published in
World Journal of Urology / Issue 1/2018
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI
https://doi.org/10.1007/s00345-017-2117-2

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