Abstract
Purpose
Recurrent pregnancy loss (RPL) is defined as the occurrence of two or more miscarriages before the 20th week of pregnancy. T helper17 cells are a novel subset of T cells, which secrete IL (Interleukin)-17 and are known to be involved in inflammation, autoimmunity and rejection of non-self tissues. Herein, we studied the association between IL-17A rs2275913 and IL-17F rs763780 gene polymorphisms with RPL in Iranian women.
Methods
A case-controlled study was performed on two groups consisting of 85 healthy women with at least one delivery and 85 women with the history of two or more RPLs. The frequency of IL-17A rs2275913 and IL-17 F rs763780 polymorphisms were determined by PCR-RFLP.
Results
In the RPL group, the genotypes frequencies of rs2275913 polymorphism were GG (8.2 %), AG (30.6 %), and AA (61.2 %) and in the control group, were GG (3.5 %), AG (42.4 %) and AA (54.1 %). Statistical analysis showed no significant difference between the genotypes of AA, AG and GG in the two groups (p = 0.1). The genotypes frequencies of rs763780 polymorphism were TT (43.5 %), TC (49.4 %) and CC (7.1 %) in the RPL group; whereas the frequencies were TT (25.9 %), TC (70.6 %) and CC (3.5 %) in the control group. Statistical analysis revealed a significant difference in the TT, TC, and CC genotypes frequencies between the case and the control groups (p = 0.01).
Conclusions
Our findings indicate that IL-17F polymorphism, rs763780, might be associated with a high risk of RPL in Iranian women.
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References
Meka A, Reddy BM. Recurrent spontaneous abortions: an overview of genetic and non-genetic backgrounds. Int J Hum Genet. 2006;6(2):109.
Stephenson MD. Frequency of factors associated with habitual abortion in 197 couples. Fertil Steril. 1996;66(1):24–9.
Toth B, Jeschke U, Rogenhofer N, Scholz C, Würfel W, Thaler CJ, et al. Recurrent miscarriage: current concepts in diagnosis and treatment. J Reprod Immunol. 2010;85(1):25–32. doi:10.1016/j.jri.2009.12.006.
Hossein H, Mahroo M, Abbas A, Firouzeh A, Nadia H. Cytokine production by peripheral blood mononuclear cells in recurrent miscarriage. Cytokine. 2004;28(2):83–6.
Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, et al. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17 + T helper cells. Cell. 2006;126:1121–33.
McGeachy MJ, Cua DJ. Th17 cell differentiation: the long and winding road. Immunity. 2008;28:445–53.
Iwakura Y, Nakae S, Saijo S, Ishigame H. The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunological reviews.2008; 226:57.79. doi:10.1111/j.1600-065×.2008.00699.x
Reynolds JM, Angkasekwinai P, Dong C.IL-17 family member cytokines: regulation and function in innate immunity. Cytokine & growth factor reviews.2010;21 (6):413–423. doi:10.1016/j.cytogfr.2010.10.002
Chang SH, Park H, Dong C. Act1 adaptor protein is an immediate and essential signaling component of interleukin-17 receptor. J Biol Chem. 2006;281(47):35603–7. doi:10.1074/jbc.C600256200.
Qian Y, Liu C, Hartupee J, Altuntas CZ, Gulen MF, Jane-Wit D, et al. The adaptor Act1 is required for interleukin 17-dependent signaling associated with autoimmune and inflammatory disease. Nat Immunol. 2007;8(3):247–56.
Nakashima A, Ito M, Shima T, Bac ND, Hidaka T, Saito S. Accumulation of IL-17-positive cells in decidua of inevitable abortion cases. Am J Reprod Immunol. 2010;64(1):4–11. doi:10.1111/j.1600-0897.2010.00812.x.
Wang WJ, Hao CF, Yi L, Yin GJ, Bao SH, Qiu LH, et al. Increased prevalence of T helper 17 (Th17) cells in peripheral blood and decidua in unexplained recurrent spontaneous abortion patients. J Reprod Immunol. 2010;84(2):164–70. doi:10.1016/j.jri.2009.12.003.
Saini V, Arora S, Yadav A, Bhattacharjee J. Cytokines in recurrent pregnancy loss. Clinica chimica acta; international journal of clinical chemistry.2011;412 (9–10):702–708. doi:10.1016/j.cca.2011.01.002
Arruvito L, Sanz M, Banham AH, Fainboim L. Expansion of CD4 + CD25 + and FOXP3+ regulatory T cells during the follicular phase of the menstrual cycle: implications for human reproduction. J Immunol. 2007;178(4):2572–8.
Yang H, Qiu L, Chen G, Ye Z, Lu C, Lin Q. Proportional change of CD4 + CD25+ regulatory T cells in decidua and peripheral blood in unexplained recurrent spontaneous abortion patients. Fertility and sterility.2008;89 (3):656–661. doi:10.1016/j.fertnstert.2007.03.037
Liu XK, Lin X, Gaffen SL. Crucial role for nuclear factor of activated T cells in T cell receptor-mediated regulation of human interleukin-17. J Biol Chem. 2004;279:52762–71.
Espinoza JL, Takami A, Nakata K, Onizuka M, Kawase T, Akiyama H, Miyamura K, Morishima Y, Fukuda T, Kodera Y, Nakao S. A genetic variant in the IL-17 promoter is functionally associated with acute graft-versus-host disease after unrelated bone marrow transplantation. PloS one.2011;6 (10):e26229. doi:10.1371/journal.pone.0026229
Kawaguchi M, Takahashi D, Hizawa N, Suzuki S, Matsukura S, Kokubu F, et al. IL-17 F sequence variant (His161Arg) is associated with protection against asthma and antagonizes wild-type IL-17 F activity. J Allergy Clin Immunol. 2006;117(4):795–801. doi:10.1016/j.jaci.2005.12.1346.
Fujino S, Andoh A, Bamba S, Ogawa A, Hata K, Araki Y, et al. Increased expression of interleukin 17 in inflammatory bowel disease. Gut. 2003;52:65–70.
Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity. 2008;28:454–67.
Nakashima A, Ito M, Yoneda S, Shiozaki A, Hidaka T, Saito S. Circulating and decidual Th17 cell levels in healthy pregnancy. Am J Reprod Immunol. 2010;63(2):104–9. doi:10.1111/j.1600-0897.2009.00771.x.
Lee SK, Kim JY, Hur SE, Kim CJ, Na BJ, Lee M, et al. An imbalance in interleukin-17-producing T and Foxp3 (+) regulatory T cells in women with idiopathic recurrent pregnancy loss. Hum Reprod. 2011;26(11):2964–71. doi:10.1093/humrep/der301.
Wang L, Jiang Y, Zhang Y, Wang Y, Huang S, Wang Z, Tian B, Yang Y, Jiang W, Pang D. Association analysis of IL-17A and IL-17 F polymorphisms in Chinese Han women with breast cancer. PloS one.2012; 7 (3):e34400. doi:10.1371/journal.pone.0034400
Quan Y, Zhou B, Wang Y, Duan R, Wang K, Gao Q, et al. Association between IL17 polymorphisms and risk of cervical cancer in Chinese women. Clin Dev Immunol. 2012;2012:258293. doi:10.1155/2012/258293.
Hayashi R, Tahara T, Shiroeda H, Matsue Y, Minato T, Nomura T, et al. Association of genetic polymorphisms in IL17A and IL17F with gastro-duodenal diseases. J Gastrointestin Liver Dis. 2012;21(3):243–9.
Paradowska-Gorycka A, Wojtecka-Lukasik E, Trefler J, Wojciechowska B, Lacki JK, Maslinski S. Association between IL-17 F gene polymorphisms and susceptibility to and severity of rheumatoid arthritis (RA). Scandinavian journal of immunology. 2010;72(2):134–41. doi:10.1111/j.1365-3083.2010.02411.x.
Shibata T, Tahara T, Hirata I, Arisawa T. Genetic polymorphism of interleukin-17A and -17 F genes in gastric carcinogenesis. Human immunology.2009;70 (7):547–551. doi:10.1016/j.humimm.2009.04.030.
Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al. The influence of polymorphisms of interleukin-17A and interleukin-17 F genes on the susceptibility to ulcerative colitis. Journal of clinical immunology. 2008;28(1):44–9. doi:10.1007/s10875-007-9125-8.
Espinoza JL, Takami A, Onizuka M, Kawase T, Sao H, Akiyama H, et al. Japan Marrow Donor Program. A single nucleotide polymorphism of IL-17 gene in the recipient is associated with acute GVHD after HLA-matched unrelated BMT. Bone Marrow Transplant. 2011;46(11):1455–63.
Acknowledgments
Shahid Sadoughi University of Medical Sciences provided the grant for this research project. This manuscript is a part of in the M.Sc thesis of Soheil Najafi. The authors are grateful to Drs. Farshid Noorbakhsh and Kazem Barzegar for their critical reading of the manuscript and Dr. Hossein Fallahzadeh for statistical assistance.
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The authors declare that they have no conflicts of interest.
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The role of IL-17 in the pathogenesis of the recurrent pregnancy loss (RPL) has remained unclear. This is first report frequency of IL-17 gene polymorphism in RPL subjects and controls in Iranian population. IL-17 F polymorphism, rs763780, might be associated with a high risk of RPL.
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Najafi, S., Hadinedoushan, H., Eslami, G. et al. Association of IL-17A and IL-17 F gene polymorphisms with recurrent pregnancy loss in Iranian women. J Assist Reprod Genet 31, 1491–1496 (2014). https://doi.org/10.1007/s10815-014-0294-0
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DOI: https://doi.org/10.1007/s10815-014-0294-0