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Khanbarari, F., Ghasemi, N., Vakili, M., & Samadi, M. (2021). Association of the single nucleotide polymorphism C1858T of the PTPN22 gene with unexplained recurrent pregnancy loss: A case-control study. International Journal of Reproductive BioMedicine (IJRM), 19(10), 873-880. https://doi.org/10.18502/ijrm.v19i10.9819
https://doi.org/10.18502/ijrm.v19i10.9819
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authors
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Fateme Khanbarari
Fateme Khanbarari
Immunology Department, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Nasrin Ghasemi
Nasrin Ghasemi
Abortion Research Center, Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
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Mahmood Vakili
Mahmood Vakili
Health Monitoring Research Center, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
-
Morteza Samadi
Morteza Samadi
Abortion Research Center, Reproductive Sciences Institute, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Published Date
- Nov 4, 2021
Association of the single nucleotide polymorphism C1858T of the PTPN22 gene with unexplained recurrent pregnancy loss: A case-control study
Abstract
Background: Lymphoid-tyrosine-phosphatase which is encoded by the protein tyrosine phosphatase non-receptor 22 (PTPN22) gene plays a pivotal role in the regulation of immune responses by dephosphorylating several signaling intermediates of immune cells.
Objective: Since a balanced immune response has been shown to be important during pregnancy, the purpose of this research was to compare the frequency of the PTPN22 C1858T polymorphism in women with unexplained recurrent pregnancy loss (URPL) vs. in a control group for the first time.
Materials and Methods: Genomic DNA from 200 individuals with URPL and 200 individuals without URPL (the control group) at the infertility center in Yazd, Iran was isolated using the salting-out method. The PTPN22 C1858T polymorphism of the two groups was analyzed using polymerase chain reaction-restriction fragment length polymorphism. Genotype frequencies in the women with URPL and the fertile control group were compared using the Chi-square test.
Results: There were significant differences in the frequency of the PTPN22 1858T polymorphism in the URPL individuals vs. the healthy controls, i.e. 32.0% and 21.5%, respectively (p = 0.01).
Conclusion: Our findings suggest that the PTPN22 1858T polymorphism could play a role in recurrent pregnancy loss. Therefore, genotyping of the mentioned polymorphism can help clinicians to predict the probable risk of URPL.
Key words: Recurrent pregnancy loss, PTPN22 protein, Single nucleotide polymorphism.
References
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[14] Burn GL, Svensson L, Sanchez-Blanco C, Saini M, Cope AP. Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? FEBS Lett 2011; 585: 3689–3698.
[15] Arechiga AF, Habib T, He Y, Zhang X, Zhang ZhY, Funk A, et al. Cutting edge: The PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. J Immunol 2009; 182: 3343–3347.
[16] Habib T, Funk A, Rieck M, Brahmandam A, Dai X, Panigrahi AK, et al. Altered B cell homeostasis is associated with type I diabetes and carriers of the PTPN22 allelic variant. J Immunol 2012; 188: 487– 496.
[17] Sharp RC, Abdulrahim M, Naser ES, Naser SA. Genetic variations of PTPN2 and PTPN22: Role in the pathogenesis of type 1 diabetes and Crohn’s disease. Front Cell Infect Microbiol 2015; 5: 95.
[18] Goulielmos GN, Chiaroni-Clarke RC, Dimopoulou DG, Zervou MI, Trachana M, Pratsidou-Gertsi P, et al. Association of juvenile idiopathic arthritis with PTPN22 rs2476601 is specific to females in a Greek population. Pediatr Rheumatol Online J 2016; 14: 25.
[19] Hersh AO, Prahalad S. Immunogenetics of juvenile idiopathic arthritis: A comprehensive review. J Autoimmun 2015; 64: 113–124.
[20] Bottini N, Peterson EJ. Tyrosine phosphatase PTPN22: Multifunctional regulator of immune signaling, development, and disease. Annu Rev Immunol 2014; 32: 83–119.
[21] Sharif K, Sharif Y, Watad A, Yavne Y, Lichtbroun B, Bragazzi NL, et al. Vitamin D, autoimmunity and recurrent pregnancy loss: More than an association. Am J Reprod Immunol 2018; 80: e12991.
[22] Wong LF, Porter TF, de Jesús GR. Recurrent early pregnancy loss and antiphospholipid antibodies: Where do we stand? Lupus 2014; 23: 1226–1228.
[23] Lu Ch, Liu Y, Jiang HL. Aspirin or heparin or both in the treatment of recurrent spontaneous abortion in women with antiphospholipid antibody syndrome: A meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med 2019; 32: 1299–1311.
[24] de Lima SC, Adelino JE, Crovella S, de Azevedo Silva J, Sandrin-Garcia P. PTPN22 1858C > T polymorphism and susceptibility to systemic lupus erythematosus: A meta-analysis update. Autoimmunity 2017; 50: 428–434.
[25] Gomes FMCS, Bianco B, Teles JS, Christofolini DM, de Souza AMB, Guedes AD, et al. PTPN22 C1858T polymorphism in women with endometriosis. Am J Reprod Immunol 2010; 63: 227–232.
[26] Pabalan N, Jarjanazi H, Christofolini DM, Bianco B, Barbosa CP. Association of the protein tyrosine phosphatase non-receptor 22 polymorphism (PTPN22) with endometriosis: A meta-analysis. Einstein (São Paulo) 2017; 15: 105–111.
[27] Abdollahi E, Tavasolian F, Ghasemi N, Mirghanizadeh SA, Azizi M, Ghoryani M, et al. Association between lower frequency of R381Q variant (rs11209026) in IL-23 receptor gene and increased risk of recurrent spontaneous abortion (RSA). J Immunotoxicol 2015; 12: 317–321.
[28] Boechat AL, Ogusku MM, Sadahiro A, dos Santos MC. Association between the PTPN22 1858C/T gene polymorphism and tuberculosis resistance. Infec Genet Evol 2013; 16: 310–313.
[29] Ghorban Kh, Ezzeddini R, Eslami M, Yousefi B, Sadighi Moghaddam B, Tahoori MT, et al. PTPN22 1858 C/T polymorphism is associated with alteration of cytokine profiles as a potential pathogenic mechanism in rheumatoid arthritis. Immunol Lett 2019; 216: 106–113.
[30] Khanbarari F, Vakili M, Samadi M. The relationship between rs2488457 polymorphism of PTPN22 gene and recurrent pregnancy loss (RPL). Iran J Obstet Gynecol Infertil 2017; 20: 49–55.
[2] Fotoohi M, Ghasemi N, Mirghanizadeh SA, Vakili M, Samadi M. Association between HLAE gene polymorphism and unexplained recurrent spontaneous abortion (RSA) in Iranian women. Int J Reprod BioMed 2016; 14: 477–482.
[3] Krieg S, Westphal L. Immune function and recurrent pregnancy loss. Semin Reprod Med 2015; 33: 305– 312.
[4] Arjmand F, Samadi M. Association of 14-bp insertion/deletion polymorphism of HLA-G gene with idiopathic recurrent miscarriages in infertility center patients in Yazd, Iran. J Immunotoxicol 2016; 13: 249–254.
[5] Tizaoui K, Kim SH, Jeong GH, Kronbichler A, Lee KS, Lee KH, et al. Association of PTPN22 1858C/T polymorphism with autoimmune diseases: A systematic review and bayesian approach. J Clin Med 2019; 8: 347.
[6] Carmona FD, Martín J. The potential of PTPN22 as a therapeutic target for rheumatoid arthritis. Exp Opin Ther Targets 2018; 22: 879–891.
[7] Takeuchi Y, Hirota K, Sakaguchi Sh. Impaired T cell receptor signaling and development of T cellmediated autoimmune arthritis. Immunol Rev 2020; 294: 164–176.
[8] Mustelin T, Bottini N, Stanford SM. The contribution of PTPN22 to Rheumatic disease. Arthritis Rheumatol 2019; 71: 486–495.
[9] Elshazli R, Settin A. Association of PTPN22 rs2476601 and STAT4 rs7574865 polymorphisms with rheumatoid arthritis: A meta-analysis update. Immunobiology 2015; 220: 1012–1024.
[10] Tang S, Peng W, Wang Ch, Tang H, Zhang Q. Association of the PTPN22 gene (+1858C/T, -1123G/C) polymorphisms with type 1 diabetes mellitus: A systematic review and meta-analysis. Diabetes Res Clin Pract 2012; 97: 446–452.
[11] Wu H, Wan S, Qu M, Ren B, Liu L, Shen H. The relationship between PTPN22 R620W polymorphisms and the susceptibility to autoimmune thyroid diseases: An updated metaanalysis. Immunol Invest 2020: 1–14.
[12] Ostanek L, Ostanek-Pańka M, Bobrowska-Snarska D, Bińczak-Kuleta A, Fischer K, Kaczmarczyk M, et al. PTPN22 1858C>T gene polymorphism in patients with SLE: Association with serological and clinical results. Mol Biol Rep 2014; 41: 6195–6200.
[13] Rawlings DJ, Dai X, Buckner JH. The role of PTPN22 risk variant in the development of autoimmunity: Finding common ground between mouse and human. J Immunol 2015; 194: 2977–2984.
[14] Burn GL, Svensson L, Sanchez-Blanco C, Saini M, Cope AP. Why is PTPN22 a good candidate susceptibility gene for autoimmune disease? FEBS Lett 2011; 585: 3689–3698.
[15] Arechiga AF, Habib T, He Y, Zhang X, Zhang ZhY, Funk A, et al. Cutting edge: The PTPN22 allelic variant associated with autoimmunity impairs B cell signaling. J Immunol 2009; 182: 3343–3347.
[16] Habib T, Funk A, Rieck M, Brahmandam A, Dai X, Panigrahi AK, et al. Altered B cell homeostasis is associated with type I diabetes and carriers of the PTPN22 allelic variant. J Immunol 2012; 188: 487– 496.
[17] Sharp RC, Abdulrahim M, Naser ES, Naser SA. Genetic variations of PTPN2 and PTPN22: Role in the pathogenesis of type 1 diabetes and Crohn’s disease. Front Cell Infect Microbiol 2015; 5: 95.
[18] Goulielmos GN, Chiaroni-Clarke RC, Dimopoulou DG, Zervou MI, Trachana M, Pratsidou-Gertsi P, et al. Association of juvenile idiopathic arthritis with PTPN22 rs2476601 is specific to females in a Greek population. Pediatr Rheumatol Online J 2016; 14: 25.
[19] Hersh AO, Prahalad S. Immunogenetics of juvenile idiopathic arthritis: A comprehensive review. J Autoimmun 2015; 64: 113–124.
[20] Bottini N, Peterson EJ. Tyrosine phosphatase PTPN22: Multifunctional regulator of immune signaling, development, and disease. Annu Rev Immunol 2014; 32: 83–119.
[21] Sharif K, Sharif Y, Watad A, Yavne Y, Lichtbroun B, Bragazzi NL, et al. Vitamin D, autoimmunity and recurrent pregnancy loss: More than an association. Am J Reprod Immunol 2018; 80: e12991.
[22] Wong LF, Porter TF, de Jesús GR. Recurrent early pregnancy loss and antiphospholipid antibodies: Where do we stand? Lupus 2014; 23: 1226–1228.
[23] Lu Ch, Liu Y, Jiang HL. Aspirin or heparin or both in the treatment of recurrent spontaneous abortion in women with antiphospholipid antibody syndrome: A meta-analysis of randomized controlled trials. J Matern Fetal Neonatal Med 2019; 32: 1299–1311.
[24] de Lima SC, Adelino JE, Crovella S, de Azevedo Silva J, Sandrin-Garcia P. PTPN22 1858C > T polymorphism and susceptibility to systemic lupus erythematosus: A meta-analysis update. Autoimmunity 2017; 50: 428–434.
[25] Gomes FMCS, Bianco B, Teles JS, Christofolini DM, de Souza AMB, Guedes AD, et al. PTPN22 C1858T polymorphism in women with endometriosis. Am J Reprod Immunol 2010; 63: 227–232.
[26] Pabalan N, Jarjanazi H, Christofolini DM, Bianco B, Barbosa CP. Association of the protein tyrosine phosphatase non-receptor 22 polymorphism (PTPN22) with endometriosis: A meta-analysis. Einstein (São Paulo) 2017; 15: 105–111.
[27] Abdollahi E, Tavasolian F, Ghasemi N, Mirghanizadeh SA, Azizi M, Ghoryani M, et al. Association between lower frequency of R381Q variant (rs11209026) in IL-23 receptor gene and increased risk of recurrent spontaneous abortion (RSA). J Immunotoxicol 2015; 12: 317–321.
[28] Boechat AL, Ogusku MM, Sadahiro A, dos Santos MC. Association between the PTPN22 1858C/T gene polymorphism and tuberculosis resistance. Infec Genet Evol 2013; 16: 310–313.
[29] Ghorban Kh, Ezzeddini R, Eslami M, Yousefi B, Sadighi Moghaddam B, Tahoori MT, et al. PTPN22 1858 C/T polymorphism is associated with alteration of cytokine profiles as a potential pathogenic mechanism in rheumatoid arthritis. Immunol Lett 2019; 216: 106–113.
[30] Khanbarari F, Vakili M, Samadi M. The relationship between rs2488457 polymorphism of PTPN22 gene and recurrent pregnancy loss (RPL). Iran J Obstet Gynecol Infertil 2017; 20: 49–55.