The Iranian Journal of Obstetrics, Gynecology and Infertility

The Iranian Journal of Obstetrics, Gynecology and Infertility

The relationship between rs2488457 Polymorphism of PTPN22 Gene and Recurrent Pregnancy Loss (RPL)

Document Type : Original Article

Authors
Fatemeh Khanbarari 1
Mahmoud Vakili 2
Morteza Samadi 3
1 M.Sc. of Immunology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
2 Associate Professor, Department of Community Medicine, Health Monitoring Research Center, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
3 Associate Professor, Department of Immunology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran. Reproductive Immunology Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
10.22038/ijogi.2017.9955
Abstract
Introduction: Recurrent Pregnancy Loss (RPL) is determined as the loss of more than two consecutive pregnancies. Several factors are involved in causing RPL. Any disorder in function of immune system leads to fetus rejection. Lymphoid-Tyrosine-Phosphatase (LYP) which is encoded by PTPN22 gene plays a pivotal role in regulation of immune responses; recently, the polymorphism of rs2488457 which is located in the promoter region of the PTPN22 gene has been discovered. This polymorphism is able to disrupt the balance of immune system by changing the PTPN22 gene expression. Since retaining the balance of immune system is of particular importance for successful pregnancy, this study was performed with aim to compare the frequency of rs2488457 polymorphism between RPL patients and normal women.
Methods: This case-control study has been conducted in 2015 on 200 recurrent pregnancy loss (RPL) patients and 200 normal individuals resorting to the infertility center of Yazd. The PCR-RFLF procedure was carried out to investigate the genotypes and the Chi-squared test was performed to inspect the rs2488457 variant frequency. The SPSS version 19 and chi-squared test were used to analyze the obtained data. p<0.05 was considered significant.
Results: The frequency of rs2488457 polymorphism was higher in RPL patients than normal women, but the difference was not statistically significant (P=0.162).
Conclusions: The rs2488457 polymorphism is not related to RPL.
Keywords
Recurrent Pregnancy Loss (RPL)
Lyp
PTPN22
  1. Farhangi H, Badiei Z. Report of some cases of recurrent pregnancy loss due to congenital deficiency of factor XIII. Iran J Obstet Gynecol Infertil 2015; 17(138):18-21. (Persian).
  2. Laird SM, Tuckerman EM, Cork BA, Linjawi S, Blakemore AI, Li TC. A review of immune cells and molecules in women with recurrent miscarriage. Hum Reprod Update 2003; 9(2):163-74.
  3. Janan A, Honarmand H, Amirmozafari N, Asgharnia M, Janan A. Distribution of cytomegalovirus infection in spontaneous abortion. Iran J Obstet Gyneocol Infertil 2014; 17(102):12-9. (Persian).
  4. Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol 2009; 2(2):76-83.
  5. Christiansen OB, Steffensen R, Nielsen HS, Varming K. Multifactorial etiology of recurrent miscarriage and its scientific and clinical implications. Gynecol Obstet Invest 2008; 66(4):257-67.
  6. Matthiesen L, Kalkunte S, Sharma S. Multiple pregnancy failures: an immunological paradigm. Am J Reprod Immunol 2012; 67(4):334-40.
  7. Larsen EC, Christiansen OB, Kolte AM, Macklon N. New insights into mechanisms behind miscarriage. BMC Med 2013; 11:154.
  8. Dawood F, Quenby S, Farquharson R. Recurrent miscarriage: an overview. Rev Gynaecol Pract 2003; 3(1):46-50.
  9. 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(23):3689-98.
  10. Lee YH, Rho YH, Choi SJ, Ji JD, Song GG, Nath SK, et al. The PTPN22 C1858T functional polymorphism and autoimmune diseases--a meta-analysis. Rheumatology (Oxford) 2007; 46(1):49-56.
  11. Rieck M, Arechiga A, Onengut-Gumuscu S, Greenbaum C, Concannon P, Buckner JH. Genetic variation in PTPN22 corresponds to altered function of T and B lymphocytes. J Immunol 2007; 179(7):4704-10.
  12. Pierer M, Kaltenhauser S, Arnold S, Wahle M, Baerwald C, Hantzschel H, et al. Association of PTPN22 1858 single-nucleotide polymorphism with rheumatoid arthritis in a German cohort: higher frequency of the risk allele in male compared to female patients. Arthritis Res Ther 2006; 8(3):R75.
  13. Chen Z, Zhang H, Xia B, Wang P, Jiang T, Song M, et al. Association of PTPN22 gene (rs2488457) polymorphism with ulcerative colitis and high levels of PTPN22 mRNA in ulcerative colitis. Int J Colorectal Dis 2013; 28(10):1351-8.
  14. Pandey MK, Rani R, Agrawal S. An update in recurrent spontaneous abortion. Arch Gynecol Obstet 2005; 272(2):95-108.
  15. Bansal AS, Bajardeen B, Shehata H, Thum MY. Recurrent miscarriage and autoimmunity. Expert Rev Clin Immunol 2011; 7(1):37-44.
  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 2011; 188(1):487-96.
  17. Ploski R, Dziunycz P, Kostrzewa G, Roszkowski PI, Barcz E, Zabek J, et al. PTPN22/LYP 1858C>T gene polymorphism and susceptibility to endometriosis in a Polish population. J Reprod Immunol 2009; 79(2):196-200.
  18. Yamada H, Atsumi T, Kato EH, Shimada S, Morikawa M, Minakami H. Prevalence of diverse antiphospholipid antibodies in women with recurrent spontaneous abortion. Fertil Steril 2003; 80(5):1276-8.
  19. Feng X, Li YZ, Zhang Y, Bao SM, Tong DW, Zhang SL, et al. Association of the PTPN22 gene (-1123G > C) polymorphism with rheumatoid arthritis in Chinese patients. Tissue Antigens 2010; 76(4):297-300.
  20. Huang JJ, Qiu YR, Li HX, Sun DH, Yang J, Yang CL. A PTPN22 promoter polymorphism -1123G>C is associated with RA pathogenesis in Chinese. Rheumatol Int 2012; 32(3):767-71.
  21. Viken MK, Olsson M, Flam ST, Forre O, Kvien TK, Thorsby E, et al. The PTPN22 promoter polymorphism -1123G>C association cannot be distinguished from the 1858C>T association in a Norwegian rheumatoid arthritis material. Tissue Antigens 2007; 70(3):190-7.
  22. Kawasaki E, Awata T, Ikegami H, Kobayashi T, Maruyama T, Nakanishi K, et al. Systematic search for single nucleotide polymorphisms in a lymphoid tyrosine phosphatase gene (PTPN22): association between a promoter polymorphism and type 1 diabetes in Asian populations. Am J Med Genet A 2006; 140(6):586-93.
  23. Liu F, Liu J, Zheng TS, Li Q, Wang C, Pan XP, et al. The -1123G>C variant of PTPN22 gene promoter is associated with latent autoimmune diabetes in adult Chinese Hans. Cell Biochem Biophys 2012; 62(2):273-9.
  24. Ammendola M, Bottini N, Pietropolli A, Saccucci P, Gloria-Bottini F. Association between PTPN22 and endometriosis. Fertil Steril 2008; 89(4):993-4.
  25. Gomes FM, Bianco B, Teles JS, Christofolini DM, de Souza AM, Guedes AD, et al. PTPN22 C1858T polymorphism in women with endometriosis. Am J Reprod Immunol 2010; 63(3):227-32.
The Iranian Journal of Obstetrics, Gynecology and Infertility
Volume 20, Issue 9
November 2017
Pages 49-55