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Published in: Journal of Assisted Reproduction and Genetics 7/2014

01-07-2014 | Genetics

Association of the IL4R single-nucleotide polymorphism I50V with recurrent spontaneous abortion (RSA)

Authors: Fataneh Tavasolian, Elham Abdollahi, Morteza Samadi

Published in: Journal of Assisted Reproduction and Genetics | Issue 7/2014

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Abstract

Background

Recurrent spontaneous abortion (RSA) is defined as three or more consecutive abortions before the 20th week of gestation. There is increasing evidence to support an immunological mechanism for the occurrence of RSA. The purpose of our study was to examine whether single-nucleotide polymorphisms (SNPs) of the interleukin-4 receptor gene IL4R influence susceptibility to, recurrent spontaneous abortion.

Materials and methods

This is a case-control study. We recruited 200 patients with RSA (case group) using established diagnostic criteria and 200, normal individuals (control group) at the fertility and infertility center in Yazd city and Isfahan city during 2012 to 2013. We screened the I50V variant in IL-4R in patients and controls by PCR-RFLF method, and we performed an association analysis between I50V variant and RSA.the data was analyzed by spss 16 software using Chi-square test.

Results

No differences in the genotype and allele frequencies of the I50V SNPs were identified between patients with RSA and healthy controls.

Conclusions

The frequency of SNP in IL-4 receptor (I50V) in patients with recurrent spontaneous abortion did not differ significantly compared with the control group. Analysis of IL4R SNP haplotypes or complex alleles suggested no dominant protection in patients with RSA.
Literature
1.
go back to reference Lim KJ, Odukoya OA, Ajjan RA, Li T-C, Weetman AP, Cooke ID. The role of T-helper cytokines in human reproduction. Fertil Steril. 2000;73(1):136–42.PubMedCrossRef Lim KJ, Odukoya OA, Ajjan RA, Li T-C, Weetman AP, Cooke ID. The role of T-helper cytokines in human reproduction. Fertil Steril. 2000;73(1):136–42.PubMedCrossRef
2.
go back to reference Lunghi L, Ferretti ME, Medici S, Biondi C, Vesce F. Control of human trophoblast function. Reprod Biol Endocrinol. 2007;5(6). Lunghi L, Ferretti ME, Medici S, Biondi C, Vesce F. Control of human trophoblast function. Reprod Biol Endocrinol. 2007;5(6).
3.
go back to reference Raghupathy R, Makhseed M, Azizieh F, Omu A, Gupta M, Farhat R. Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. Hum Reprod. 2000;15(3):713–8.PubMedCrossRef Raghupathy R, Makhseed M, Azizieh F, Omu A, Gupta M, Farhat R. Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. Hum Reprod. 2000;15(3):713–8.PubMedCrossRef
4.
go back to reference Rezaei A, Dabbagh A. T-helper (1) cytokines increase during early pregnancy in women with a history of recurrent spontaneous abortion. Med Sci Monit. 2002;8(8):CR607–CR10.PubMed Rezaei A, Dabbagh A. T-helper (1) cytokines increase during early pregnancy in women with a history of recurrent spontaneous abortion. Med Sci Monit. 2002;8(8):CR607–CR10.PubMed
5.
go back to reference Sasaki Y, Sakai M, Miyazaki S, Higuma S, Shiozaki A, Saito S. Decidual and peripheral blood CD4+ CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod. 2004;10(5):347–53.PubMedCrossRef Sasaki Y, Sakai M, Miyazaki S, Higuma S, Shiozaki A, Saito S. Decidual and peripheral blood CD4+ CD25+ regulatory T cells in early pregnancy subjects and spontaneous abortion cases. Mol Hum Reprod. 2004;10(5):347–53.PubMedCrossRef
6.
go back to reference Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441(7090):235–8.PubMedCrossRef Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature. 2006;441(7090):235–8.PubMedCrossRef
7.
go back to reference Saito S, Nakashima A, Shima T, Ito MREVIEWARTICLE. Th1/Th2/Th17 and Regulatory T‐Cell Paradigm in Pregnancy. Am J Reprod Immunol. 2010;63(6):601–10.PubMedCrossRef Saito S, Nakashima A, Shima T, Ito MREVIEWARTICLE. Th1/Th2/Th17 and Regulatory T‐Cell Paradigm in Pregnancy. Am J Reprod Immunol. 2010;63(6):601–10.PubMedCrossRef
8.
go back to reference Nakashima A, Ito M, Yoneda S, Shiozaki A, Hidaka T, Saito S. SHORT COMMUNICATION: Circulating and Decidual Th17 Cell Levels in Healthy Pregnancy. Am J Reprod Immunol. 2010;63(2):104–9.PubMedCrossRef Nakashima A, Ito M, Yoneda S, Shiozaki A, Hidaka T, Saito S. SHORT COMMUNICATION: Circulating and Decidual Th17 Cell Levels in Healthy Pregnancy. Am J Reprod Immunol. 2010;63(2):104–9.PubMedCrossRef
9.
go back to reference Korn T, Mitsdoerffer M, Croxford AL, Awasthi A, Dardalhon VA, Galileos G, et al. IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells. Proc Natl Acad Sci. 2008;105(47):18460–5.PubMedCentralPubMedCrossRef Korn T, Mitsdoerffer M, Croxford AL, Awasthi A, Dardalhon VA, Galileos G, et al. IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional T cells into Foxp3+ regulatory T cells. Proc Natl Acad Sci. 2008;105(47):18460–5.PubMedCentralPubMedCrossRef
10.
go back to reference Steinman L. A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell–mediated tissue damage. Nat Med. 2007;13(2):139–45.PubMedCrossRef Steinman L. A brief history of TH17, the first major revision in the TH1/TH2 hypothesis of T cell–mediated tissue damage. Nat Med. 2007;13(2):139–45.PubMedCrossRef
11.
go back to reference Afzali B, Lombardi G, Lechler R, Lord G. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol. 2007;148(1):32–46.PubMedCentralPubMedCrossRef Afzali B, Lombardi G, Lechler R, Lord G. The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin Exp Immunol. 2007;148(1):32–46.PubMedCentralPubMedCrossRef
12.
go back to reference Wang W-J, Hao C-F, Yin G-J, Bao S-H, Qiu L-H, Lin Q-D. 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.PubMedCrossRef Wang W-J, Hao C-F, Yin G-J, Bao S-H, Qiu L-H, Lin Q-D. 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.PubMedCrossRef
13.
go back to reference Kruse S, Japha T, Tedner M, Sparholt S, Forster J, Kuehr J, et al. The polymorphisms S503P and Q576R in the interleukin-4 receptor gene are associated with atopy and influence the signal transduction. IMMUNOL-OXFORD-. 1999;96:365–71.CrossRef Kruse S, Japha T, Tedner M, Sparholt S, Forster J, Kuehr J, et al. The polymorphisms S503P and Q576R in the interleukin-4 receptor gene are associated with atopy and influence the signal transduction. IMMUNOL-OXFORD-. 1999;96:365–71.CrossRef
14.
go back to reference Risma KA, Wang N, Andrews RP, Cunningham CM, Ericksen MB, Bernstein JA, et al. V75R576 IL-4 receptor α is associated with allergic asthma and enhanced IL-4 receptor function. J Immunol. 2002;169(3):1604–10.PubMedCrossRef Risma KA, Wang N, Andrews RP, Cunningham CM, Ericksen MB, Bernstein JA, et al. V75R576 IL-4 receptor α is associated with allergic asthma and enhanced IL-4 receptor function. J Immunol. 2002;169(3):1604–10.PubMedCrossRef
15.
go back to reference Mellor A, Munn D. Immunology at the maternal-fetal interface: lessons for T cell tolerance and suppression. Annu Rev Immunol. 2000;18(1):367–91.PubMedCrossRef Mellor A, Munn D. Immunology at the maternal-fetal interface: lessons for T cell tolerance and suppression. Annu Rev Immunol. 2000;18(1):367–91.PubMedCrossRef
16.
go back to reference Soares MJ. The prolactin and growth hormone families: pregnancy-specific hormones/cytokines at the maternal-fetal interface. Reprod Biol Endocrinol. 2004;2(10.1186):1477–7827. Soares MJ. The prolactin and growth hormone families: pregnancy-specific hormones/cytokines at the maternal-fetal interface. Reprod Biol Endocrinol. 2004;2(10.1186):1477–7827.
17.
go back to reference Kwak‐Kim J, Yang KM, Gilman‐Sachs A. Recurrent pregnancy loss: a disease of inflammation and coagulation. J Obstet Gynaecol Res. 2009;35(4):609–22.PubMedCrossRef Kwak‐Kim J, Yang KM, Gilman‐Sachs A. Recurrent pregnancy loss: a disease of inflammation and coagulation. J Obstet Gynaecol Res. 2009;35(4):609–22.PubMedCrossRef
18.
go back to reference Boyson JE, Rybalov B, Koopman LA, Exley M, Balk SP, Racke FK, et al. CD1d and invariant NKT cells at the human maternal–fetal interface. Proc Natl Acad Sci. 2002;99(21):13741–6.PubMedCentralPubMedCrossRef Boyson JE, Rybalov B, Koopman LA, Exley M, Balk SP, Racke FK, et al. CD1d and invariant NKT cells at the human maternal–fetal interface. Proc Natl Acad Sci. 2002;99(21):13741–6.PubMedCentralPubMedCrossRef
19.
go back to reference Entrican G. Immune regulation during pregnancy and host–pathogen interactions in infectious abortion. J Comp Pathol. 2002;126(2):79–94.PubMedCrossRef Entrican G. Immune regulation during pregnancy and host–pathogen interactions in infectious abortion. J Comp Pathol. 2002;126(2):79–94.PubMedCrossRef
20.
go back to reference Hunt JS, Petroff MG, McIntire RH, Ober C. HLA-G and immune tolerance in pregnancy. FASEB J. 2005;19(7):681–93.PubMedCrossRef Hunt JS, Petroff MG, McIntire RH, Ober C. HLA-G and immune tolerance in pregnancy. FASEB J. 2005;19(7):681–93.PubMedCrossRef
21.
go back to reference Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol. 2009;27:485–517.PubMedCrossRef Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol. 2009;27:485–517.PubMedCrossRef
22.
go back to reference Mandal M, Marzouk AC, Donnelly R, Ponzio NM. Maternal immune stimulation during pregnancy affects adaptive immunity in offspring to promote development of TH17 cells. Brain Behav Immun. 2011;25(5):863–71.PubMedCrossRef Mandal M, Marzouk AC, Donnelly R, Ponzio NM. Maternal immune stimulation during pregnancy affects adaptive immunity in offspring to promote development of TH17 cells. Brain Behav Immun. 2011;25(5):863–71.PubMedCrossRef
23.
go back to reference Lee SK, Kim JY, Lee M. Gilman‐Sachs A, Kwak‐Kim J. Th17 and regulatory T cells in women with recurrent pregnancy loss. Am J Reprod Immunol. 2012;67(4):311–8.PubMedCrossRef Lee SK, Kim JY, Lee M. Gilman‐Sachs A, Kwak‐Kim J. Th17 and regulatory T cells in women with recurrent pregnancy loss. Am J Reprod Immunol. 2012;67(4):311–8.PubMedCrossRef
24.
go back to reference Numasaki M. Fukushi J-i, Ono M, Narula SK, Zavodny PJ, Kudo T, et al. Interleukin-17 promotes angiogenesis and tumor growth. Blood. 2003;101(7):2620–7.PubMedCrossRef Numasaki M. Fukushi J-i, Ono M, Narula SK, Zavodny PJ, Kudo T, et al. Interleukin-17 promotes angiogenesis and tumor growth. Blood. 2003;101(7):2620–7.PubMedCrossRef
25.
go back to reference Pongcharoen S, Somran J, Sritippayawan S, Niumsup P, Chanchan P, Butkhamchot P, et al. Interleukin-17 expression in the human placenta. Placenta. 2007;28(1):59–63.PubMedCrossRef Pongcharoen S, Somran J, Sritippayawan S, Niumsup P, Chanchan P, Butkhamchot P, et al. Interleukin-17 expression in the human placenta. Placenta. 2007;28(1):59–63.PubMedCrossRef
26.
go back to reference Liu YS, Wu L, Tong XH, Wu LM, He GP, Zhou GX, et al. Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion. Am J Reprod Immunol. 2011;65(5):503–11.PubMedCrossRef Liu YS, Wu L, Tong XH, Wu LM, He GP, Zhou GX, et al. Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion. Am J Reprod Immunol. 2011;65(5):503–11.PubMedCrossRef
27.
go back to reference NG SC, GILMAN‐SACHS A, THAKER P, BEAMAN KD, BEER AE, KWAK‐KIM J. Expression of intracellular Th1 and Th2 cytokines in women with recurrent spontaneous abortion, implantation failures after IVF/ET or normal pregnancy. Am J Reprod Immunol. 2002;48(2):77–86.PubMedCrossRef NG SC, GILMAN‐SACHS A, THAKER P, BEAMAN KD, BEER AE, KWAK‐KIM J. Expression of intracellular Th1 and Th2 cytokines in women with recurrent spontaneous abortion, implantation failures after IVF/ET or normal pregnancy. Am J Reprod Immunol. 2002;48(2):77–86.PubMedCrossRef
28.
go back to reference Lee YK, Mukasa R, Hatton RD, Weaver CT. Developmental plasticity of Th17 and Treg cells. Curr Opin Immunol. 2009;21(3):274–80.PubMedCrossRef Lee YK, Mukasa R, Hatton RD, Weaver CT. Developmental plasticity of Th17 and Treg cells. Curr Opin Immunol. 2009;21(3):274–80.PubMedCrossRef
29.
go back to reference Saito S, Sasaki Y, Sakai M. CD4 < sup > +</sup > CD25 < sup > high</sup > regulatory T cells in human pregnancy. J Reprod Immunol. 2005;65(2):111–20.PubMedCrossRef Saito S, Sasaki Y, Sakai M. CD4 < sup > +</sup > CD25 < sup > high</sup > regulatory T cells in human pregnancy. J Reprod Immunol. 2005;65(2):111–20.PubMedCrossRef
30.
go back to reference Santner-Nanan B, Peek MJ, Khanam R, Richarts L, Zhu E, de St Groth BF, et al. Systemic increase in the ratio between Foxp3+ and IL-17-producing CD4+ T cells in healthy pregnancy but not in preeclampsia. J Immunol. 2009;183(11):7023–30.PubMedCrossRef Santner-Nanan B, Peek MJ, Khanam R, Richarts L, Zhu E, de St Groth BF, et al. Systemic increase in the ratio between Foxp3+ and IL-17-producing CD4+ T cells in healthy pregnancy but not in preeclampsia. J Immunol. 2009;183(11):7023–30.PubMedCrossRef
31.
go back to reference Dimitriadis E, White C, Jones R, Salamonsen L. Cytokines, Chemokines and growth factors in endometrium related to implantation. Hum Reprod Update. 2005;11(6):613–30.PubMedCrossRef Dimitriadis E, White C, Jones R, Salamonsen L. Cytokines, Chemokines and growth factors in endometrium related to implantation. Hum Reprod Update. 2005;11(6):613–30.PubMedCrossRef
32.
go back to reference Jerzak M, Bischof P. Apoptosis in the first trimester human placenta: the role in maintaining immune privilege at the maternal–fetal interface and in the trophoblast remodeling. Eur J Obstet Gynecol Reprod Biol. 2002;100(2):138–42.PubMedCrossRef Jerzak M, Bischof P. Apoptosis in the first trimester human placenta: the role in maintaining immune privilege at the maternal–fetal interface and in the trophoblast remodeling. Eur J Obstet Gynecol Reprod Biol. 2002;100(2):138–42.PubMedCrossRef
33.
go back to reference W-p Z, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997;89(4):587–96.CrossRef W-p Z, Flavell RA. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell. 1997;89(4):587–96.CrossRef
34.
go back to reference Skapenko A, Leipe J, Niesner U, Devriendt K, Beetz R, Radbruch A, et al. GATA-3 in human T cell helper type 2 development. J Exp Med. 2004;199(3):423–8.PubMedCentralPubMedCrossRef Skapenko A, Leipe J, Niesner U, Devriendt K, Beetz R, Radbruch A, et al. GATA-3 in human T cell helper type 2 development. J Exp Med. 2004;199(3):423–8.PubMedCentralPubMedCrossRef
35.
go back to reference Wallis SK, Cooney LA, Endres JL, Lee MJ, Ryu J, Somers EC, et al. A polymorphism in the interleukin-4 receptor affects the ability of interleukin-4 to regulate Th17 cells: a possible immunoregulatory mechanism for genetic control of the severity of rheumatoid arthritis. Arthritis Res Ther. 2011;13(1):R15.PubMedCentralPubMedCrossRef Wallis SK, Cooney LA, Endres JL, Lee MJ, Ryu J, Somers EC, et al. A polymorphism in the interleukin-4 receptor affects the ability of interleukin-4 to regulate Th17 cells: a possible immunoregulatory mechanism for genetic control of the severity of rheumatoid arthritis. Arthritis Res Ther. 2011;13(1):R15.PubMedCentralPubMedCrossRef
Metadata
Title
Association of the IL4R single-nucleotide polymorphism I50V with recurrent spontaneous abortion (RSA)
Authors
Fataneh Tavasolian
Elham Abdollahi
Morteza Samadi
Publication date
01-07-2014
Publisher
Springer US
Published in
Journal of Assisted Reproduction and Genetics / Issue 7/2014
Print ISSN: 1058-0468
Electronic ISSN: 1573-7330
DOI
https://doi.org/10.1007/s10815-014-0234-z

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