Relationship between TIM-3 gene polymorphisms and steroid-resistant primary nephrotic syndrome in children

Jing Lei; Songdong Ma

doi:10.14715/cmb/2020.66.7.12

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Vol. 66 No. 7: Issue 7

Issue Published : November 9, 2020

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Relationship between TIM-3 gene polymorphisms and steroid-resistant primary nephrotic syndrome in children

https://doi.org/10.14715/cmb/2020.66.7.12

Jing Lei

The Ninth Pediatrics, Hunan Provincial People's Hospital(The first-affiliated hospital of Hunan normal university), Changsha, Hunan410016, China.

Songdong Ma

The Ninth Pediatrics, Hunan Provincial People's Hospital(The first-affiliated hospital of Hunan normal university), Changsha, Hunan410016, China

Corresponding Author(s) : Jing Lei

441676689@qq.com

Cellular and Molecular Biology, Vol. 66 No. 7: Issue 7
Article Published : October 31, 2020

Abstract

Nephrotic syndrome, also known as nephrosis, is a collection of symptoms in medicine and urology caused by damage to the basement membrane of the kidney glomeruli and the kidneys excrete a large amount of protein. This experiment was carried out to investigate the association of three single nucleotide polymorphisms (SNPs) of T-cell immunoglobulin and mucin-domain-containing-3 (Tim-3) with childhood primary nephrotic syndrome (PNS) steroid response in Han Chinese. For this purpose, a total of 218 children with steroid-resistant PNS and 189 children with steroid-responsive PNS were enrolled in this case-control study. Three single nucleotide polymorphisms (SNPs) of the TIM-3 gene promoter region (rs4704853, rs1051746, and rs10053538) were analyzed by polymerase chain reaction (PCR) and restriction enzyme digestion. Results showed that there were 124 males and 94 females in the steroid-resistant PNS group and 114 males and 75 females in the steroid-responsive PNS group. The mean ages of the two groups were 7.9 years and 7.7 years, respectively. The distribution of alleles of Rs1051746 and Rs10053538 were significantly different between the steroid-resistant PNS group and the steroid-responsive PNS group (P-value = 0.047 and 0.012, respectively). The distribution of their genotypes was also significantly different between the steroid-resistant PNS group and the steroid-responsive PNS group (P-value = 0.044 and 0.010, respectively). Haplotype G-C-G was less frequent among steroid-resistant PNS children than the steroid-responsive PNS children (P = 0.015). There was no significant difference between the three SNPs of TIM-3 and the clinical features of these PNS children (P>0.05). It concluded that this study provided evidence showing that the polymorphisms of Rs1051746 and Rs10053538 at the TIM-3 gene were related to childhood PNS steroid response. This result provided fundamental support for future studies on the role of TIM-3 in pathogenesis and therapy of childhood PNS.

Keywords

Nephrotic syndrome Mucin-domain-containing-3 Single nucleotide polymorphisms.

Lei, J., & Ma, S. (2020). Relationship between TIM-3 gene polymorphisms and steroid-resistant primary nephrotic syndrome in children. Cellular and Molecular Biology, 66(7), 72–75. https://doi.org/10.14715/cmb/2020.66.7.12

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References

Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. Aug 23 2003; 362(9384): 629-639.
Lee DY, Kim W, Kang SK, Koh GY, Park SK. Angiotensin-converting enzyme gene polymorphism in patients with minimal-change nephrotic syndrome and focal segmental glomerulosclerosis. Nephron. 1997; 77(4): 471-473.
Wasilewska A, Zalewski G, Chyczewski L, Zoch-Zwierz W. MDR-1 gene polymorphisms and clinical course of steroid-responsive nephrotic syndrome in children. Pediatr Nephrol. Jan 2007; 22(1): 44-51.
Oktem F, Sirin A, Bilge I, Emre S, Agachan B, Ispir T. ACE I/D gene polymorphism in primary FSGS and steroid-sensitive nephrotic syndrome. Pediatr Nephrol. Apr 2004; 19(4): 384-389.
Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, Zalewski I, Imm A, Ruf EM, Mucha B, Bagga A, Neuhaus T, Fuchshuber A, Bakkaloglu A, Hildebrandt F. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol. Mar 2004; 15(3): 722-732.
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Hastings WD, Anderson DE, Kassam N, Koguchi K, Greenfield EA, Kent SC, Zheng XX, Strom TB, Hafler DA, Kuchroo VK. TIM-3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. Eur J Immunol. Sep 2009; 39(9): 2492-2501.
Gorman JV, Starbeck-Miller G, Pham NL, Traver GL, Rothman PB, Harty JT, Colgan JD. Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection. J Immunol. Apr 01 2014; 192(7): 3133-3142.
Sanchez-Fueyo A, Tian J, Picarella D, Domenig C, Zheng XX, Sabatos CA, Manlongat N, Bender O, Kamradt T, Kuchroo VK, Gutierrez-Ramos JC, Coyle AJ, Strom TB. Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance. Nat Immunol. Nov 2003; 4(11): 1093-1101.
Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. Dec 2005; 6(12): 1245-1252.
Cai XZ, Liu N, Qiao Y, Du SY, Chen Y, Chen D, Yu S, Jiang Y. Decreased TIM-3 mRNA expression in peripheral blood mononuclear cells from nephropathy patients. Genet Mol Res. Jun 12 2015; 14(2): 6543-6548.
Chae SC, Park YR, Shim SC, Yoon KS, Chung HT. The polymorphisms of Th1 cell surface gene Tim-3 are associated in a Korean population with rheumatoid arthritis. Immunol Lett. Aug 15 2004; 95(1): 91-95.
Behfarjam F, Rostamzadeh J, Zarei MA, Nikkhoo B. Association of two polymorphic codons in P53 and ABCC1 promoter with prostate cancer. Iran J Biotechnol. 2015; 13(1): 49-51.
Sheikhvatan M, Boroumand MA, Behmanesh M, Ziaee S, Cheraghee S. Integrin Beta-3 Gene Polymorphism and Risk for Myocardial Infarction in Premature Coronary Disease. Iran J Biotechnol. 2019; 17(2).
Aghamiri A, Mehrabi R, Talebi R. Genetic diversity of Pyrenophera tritici-repentis isolates, the causal agent of wheat tan spot disease from Northern Iran. Iran J Biotechnol. 2015; 13(2): 39.
Ismaili A, Yari K, Moradi M-T, Sohrabi M, Kahrizi D, Kazemi E, Souri Z. IL-1B (C+ 3954T) gene polymorphism and susceptibility to gastric cancer in the Iranian population. Asian Pac J Cancer Prev. 2015; 16: 841-844.
Mirmoayedi A, Kahrizi D, Ebadi AA, Yari K, Mohammadi M. Study of individual and sex genetic diversity among each genus and between two genera of Chrysopa and Chrysoperla (Neuroptera, Chrysopidae) based on RAPD-PCR polymorphism. Mol Biol Rep. 2012; 39(9): 8999-9006.
Yang JY, Yao Y. Classification, diagnosis and treatment of childhood glomerular disease. Chinese Journal of Pediatrics. 2001; 12.
Ghaheri M, Kahrizi D, Yari K, Babaie A, Suthar R, Kazemi E. A comparative evaluation of four DNA extraction protocols from whole blood sample. Cell Mol Biol. 2016; 62(3): 120-124.
Chen Y, Schieppati A, Chen X, Cai G, Zamora J, Giuliano GA, Braun N, Perna A. Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. Oct 16 2014; (10): Cd004293.
Hahn D, Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. Mar 18 2015; (3): Cd001533.
Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, Miura K, Aya K, Nakanishi K, Ohtomo Y, Takahashi S, Tanaka R, Kaito H, Nakamura H, Ishikura K, Ito S, Ohashi Y. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. Oct 04 2014; 384(9950): 1273-1281.
Ito S, Kamei K, Ogura M, Udagawa T, Fujinaga S, Saito M, Sako M, Iijima K. Survey of rituximab treatment for childhood-onset refractory nephrotic syndrome. Pediatr Nephrol. Feb 2013; 28(2): 257-264.

References

Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet. Aug 23 2003; 362(9384): 629-639.

Lee DY, Kim W, Kang SK, Koh GY, Park SK. Angiotensin-converting enzyme gene polymorphism in patients with minimal-change nephrotic syndrome and focal segmental glomerulosclerosis. Nephron. 1997; 77(4): 471-473.

Wasilewska A, Zalewski G, Chyczewski L, Zoch-Zwierz W. MDR-1 gene polymorphisms and clinical course of steroid-responsive nephrotic syndrome in children. Pediatr Nephrol. Jan 2007; 22(1): 44-51.

Oktem F, Sirin A, Bilge I, Emre S, Agachan B, Ispir T. ACE I/D gene polymorphism in primary FSGS and steroid-sensitive nephrotic syndrome. Pediatr Nephrol. Apr 2004; 19(4): 384-389.

Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, Zalewski I, Imm A, Ruf EM, Mucha B, Bagga A, Neuhaus T, Fuchshuber A, Bakkaloglu A, Hildebrandt F. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol. Mar 2004; 15(3): 722-732.

Monney L, Sabatos CA, Gaglia JL, Ryu A, Waldner H, Chernova T, Manning S, Greenfield EA, Coyle AJ, Sobel RA, Freeman GJ, Kuchroo VK. Th1-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature. Jan 31 2002; 415(6871): 536-541.

Hastings WD, Anderson DE, Kassam N, Koguchi K, Greenfield EA, Kent SC, Zheng XX, Strom TB, Hafler DA, Kuchroo VK. TIM-3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines. Eur J Immunol. Sep 2009; 39(9): 2492-2501.

Gorman JV, Starbeck-Miller G, Pham NL, Traver GL, Rothman PB, Harty JT, Colgan JD. Tim-3 directly enhances CD8 T cell responses to acute Listeria monocytogenes infection. J Immunol. Apr 01 2014; 192(7): 3133-3142.

Sanchez-Fueyo A, Tian J, Picarella D, Domenig C, Zheng XX, Sabatos CA, Manlongat N, Bender O, Kamradt T, Kuchroo VK, Gutierrez-Ramos JC, Coyle AJ, Strom TB. Tim-3 inhibits T helper type 1-mediated auto- and alloimmune responses and promotes immunological tolerance. Nat Immunol. Nov 2003; 4(11): 1093-1101.

Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. Dec 2005; 6(12): 1245-1252.

Cai XZ, Liu N, Qiao Y, Du SY, Chen Y, Chen D, Yu S, Jiang Y. Decreased TIM-3 mRNA expression in peripheral blood mononuclear cells from nephropathy patients. Genet Mol Res. Jun 12 2015; 14(2): 6543-6548.

Chae SC, Park YR, Shim SC, Yoon KS, Chung HT. The polymorphisms of Th1 cell surface gene Tim-3 are associated in a Korean population with rheumatoid arthritis. Immunol Lett. Aug 15 2004; 95(1): 91-95.

Behfarjam F, Rostamzadeh J, Zarei MA, Nikkhoo B. Association of two polymorphic codons in P53 and ABCC1 promoter with prostate cancer. Iran J Biotechnol. 2015; 13(1): 49-51.

Sheikhvatan M, Boroumand MA, Behmanesh M, Ziaee S, Cheraghee S. Integrin Beta-3 Gene Polymorphism and Risk for Myocardial Infarction in Premature Coronary Disease. Iran J Biotechnol. 2019; 17(2).

Aghamiri A, Mehrabi R, Talebi R. Genetic diversity of Pyrenophera tritici-repentis isolates, the causal agent of wheat tan spot disease from Northern Iran. Iran J Biotechnol. 2015; 13(2): 39.

Ismaili A, Yari K, Moradi M-T, Sohrabi M, Kahrizi D, Kazemi E, Souri Z. IL-1B (C+ 3954T) gene polymorphism and susceptibility to gastric cancer in the Iranian population. Asian Pac J Cancer Prev. 2015; 16: 841-844.

Mirmoayedi A, Kahrizi D, Ebadi AA, Yari K, Mohammadi M. Study of individual and sex genetic diversity among each genus and between two genera of Chrysopa and Chrysoperla (Neuroptera, Chrysopidae) based on RAPD-PCR polymorphism. Mol Biol Rep. 2012; 39(9): 8999-9006.

Yang JY, Yao Y. Classification, diagnosis and treatment of childhood glomerular disease. Chinese Journal of Pediatrics. 2001; 12.

Ghaheri M, Kahrizi D, Yari K, Babaie A, Suthar R, Kazemi E. A comparative evaluation of four DNA extraction protocols from whole blood sample. Cell Mol Biol. 2016; 62(3): 120-124.

Chen Y, Schieppati A, Chen X, Cai G, Zamora J, Giuliano GA, Braun N, Perna A. Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome. Cochrane Database Syst Rev. Oct 16 2014; (10): Cd004293.

Hahn D, Hodson EM, Willis NS, Craig JC. Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev. Mar 18 2015; (3): Cd001533.

Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, Miura K, Aya K, Nakanishi K, Ohtomo Y, Takahashi S, Tanaka R, Kaito H, Nakamura H, Ishikura K, Ito S, Ohashi Y. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. Oct 04 2014; 384(9950): 1273-1281.

Ito S, Kamei K, Ogura M, Udagawa T, Fujinaga S, Saito M, Sako M, Iijima K. Survey of rituximab treatment for childhood-onset refractory nephrotic syndrome. Pediatr Nephrol. Feb 2013; 28(2): 257-264.

Author biographies is not available.