OJOG  Vol.3 No.5 B , July 2013
A variant in interleukin-2 gene is associated with repeated spontaneous abortion in Ningxia Han people

Background: Recurrent spontaneous abortion (RSA) is defined as the occurrence of three or more consecutive spontaneous abortion prior to 20 weeks from the last menstrual period. It affects approximately 1% to 2% of women, and about 40% - 80% of RSA are still remained unexplained. In recent years, a lot of studies suggest that RSA is caused by the immune factors. T helper 1(Th1)-type immunity is associated with unsuccessful pregnancy especially in women with RSA, while Th2-type immunity is associated with pregnancy success. Interleukin (IL)-2 may influence Th1/Th2 immune responsiveness and has been implicated association with RSA. Aim: The aim of this study was to investigate the association of the interleukin 2 (IL-2) promoter polymorphisms at the site 330 A/C (rs2069762) with RSA. Methods: The study group comprised 189 women with RSA, and the control group consisted of 187 healthy pregnant women. Gene polymorphisms were detected by the technique of polymerase chain reaction restriction fragment length polymorphism. Results: The frequency of genotype 330C/C was significant higher (χ2 = 7.266, p = 0.007, OR = 0.362, 95% CI = 0.169 - 0.777) in the control group than in the patient group. And the frequency of the -330Aallele was significant higher (χ2 = 11.862, p = 0.001, OR = 1.741, 95% CI = 1.268 - 2.389) in the patient group than in the control group. Conclusions: This study indicated that the IL-2-330Aallele may be considered as a risk factor for RSA. CA mutation is may associated with RSA in Ningxia Han people.

Cite this paper
Pei, L. , Yang, F. , Zhang, C. , Guo, M. , Bao, J. , Lu, H. and Huo, Z. (2013) A variant in interleukin-2 gene is associated with repeated spontaneous abortion in Ningxia Han people. Open Journal of Obstetrics and Gynecology, 3, 32-36. doi: 10.4236/ojog.2013.35A2006.
[1]   Alberman, E. (1988) The epidemiology of repeated abortion. In: Beard, R.W. and Sharp, F., Eds., Early pregnancy loss: Mechanisms of treatment, Springer-Verlag, London, 9-17. doi:10.1007/978-1-4471-1658-5_2

[2]   Clifford, K., Rai, R. and Watson, H., et al. (1994) An informative protocol for the investigation of recurrent miscarriage: Preliminary experience of 500 consecutive cases. Human Reproduction, 9, 1328-1332. http://www.ncbi.nlm.nih.gov/pubmed/7962442

[3]   Holly, B., Ford, M.D., Danny, J., Schust, M.D., et al. (2009) Recurrent pregnancy loss: Etiology, diagnosis, and therapy. Reviews in Obstetrics and Gynecology, 2, 76-83. http://www.ncbi.nlm.nih. gov/pmc/articles/PMC2709325/

[4]   Vassiliadou, N., Searle, R.F. and Bulmer, J.N. (1999) Elevated expression of activation molecules by decidual lymphocytes in women suffering spontaneous early pregnancy loss. Human Reproduction, 14, 1994-1200. doi:10.1093/humrep/14.5.1194

[5]   Reghupathy, R., Makhseed, M., Azizieh, F., et al. (2000) Cytokine production by maternal lymphocytes during normal human pregnancy and in unexplained recurrent spontaneous abortion. Human Reproduction, 15, 713-718. doi:10.1093/humrep/15.3.713

[6]   Beer, A.E., Kwak, J.Y.H., Ruize, J.E., et al. (1996) Immunophenotypic profiles of peripheral blood lymphocytes in women with recurrent prefnancy looses and in fertile women with multiple failed in vitro fertilization cycles. American Journal of Reproductive Immunology, 35, 376-382. doi:10.1111/j.1600-0897.1996.tb00497.x

[7]   Leung, S.T., Derecka, K., Mann, C.E., et al. (2000) Uterine lymphocyte distribution and interleukin expression during early pregnancy in cows. Journal of Reproduction and Infertility, 119, 25-33. http://www.reproduction-online.org/content/119/1/25.long

[8]   Raghupathy, R. (1997) Th1-type immunity is incompatible with successful pregnancy. Immunology Today, 18, 478-482. doi:10.1016/S0167-5699(97)01127-4

[9]   Kidd, P. (2003) Th1/Th2 balance: The hypothesis, its limitations, and implications for health and disease. Alternative Medicine Review, 8, 223-246. http://www.altmedrev.com/publica tions/8/3/223.pdf

[10]   Peter, M., Emmer, P.M., Nelen, W.L.O.M., et al. (2000) Peripheral natural killer cytotoxicity and CD56 (+) CD16 (—) cellsincrease during early pregnancy in women with a history of recurrent spontaneous abortion. Human Reproduction, 15, 1163-1169. doi:10.1093/humrep/15.5.1163

[11]   Makhseed, M., Raghupathy, R., Azizieh, F., et al. (1999) Mitogen-induced cytokine responses of maternal peripheral blood lymphocytes indicate a differential Th-type bias in normal pregnancy and pregnancy failure. American Journal of Reproductive Immunology, 42, 273-281. doi:10.1111/j.1600-0897.1999.tb00101.x

[12]   Kwak-Kim, J.Y., Chung-Bang, H.S., Ng, S.C., et al. (2003) Increased T helper 1 cytokine responses by circulating T cells are present in women with recurrent pregnancy losses and in infertile women with multiple implantation failures after IVF. Human Reproduction, 18, 767-773. doi:10.1093/ humrep/deg156

[13]   Makhseed, M., Raghupathy, R., Azizieh, F., et al. (2001) Th1 and Th2 cytokine profiles in recurrent aborters with successful pregnancy and with subsequent abortions. Human Reproduction, 16, 2219-2226. doi:10.1093/humrep/16.10.2219

[14]   Oppenheim, J.J. (1986) Interleukins and interferons in inflammation. The Upjohn Company, Kalamazoo.

[15]   Rezaei, A. and Dabbagh, A. (2002) T-helper (1) cytokines increase during early pregnancy in women with a history of recurrent spontaneous abortion. Medical Science Monitor, 8, 607-610. http://www.ncbi.nlm.nih.gov/pubmed/12165750

[16]   Taylor, D.D., Bohler, H.C., Gercel-Taylor, C., et al. (2006) Pregnancy-linked suppression of TcR signaling pathways by a circulating factor absent in recurrent spontaneous pregnancy loss (RPL). Molecular Immunology, 43, 1872-1880. doi:10.1016/j.molimm.2005.10.008

[17]   Shang, D.K., Zheng, X.Q., Yan, W.H., et al. (2008) The significance of the serum Th1/Th2 cytokine leves in the recurrent spontaneous abortions. Chinese Journal of Birth Health & Heredity, 16, 25-26. http://en.cnki.com.cn/Article_en/CJFDTOTAL-ZYYA200804011.htm

[18]   Fu, W.Q. and Sill, B. (2007) Correlation of T lymphocyte subsets and serum IL-2, IL-10 with spontaneous abortion. Jiangsu Medical Journal, 33, 328-329. http://lib.cqvip.com/qk/ 93304X/200704/24303960.html

[19]   Mallmann, P., Mallmann, R. and Krebs, D. (1991) Determination of tumor necrosis factor alpha and interleukin 2 in women with idiopathic recurrent miscarriage. Archives of Gynecology and Obstetrics, 249, 73-78. doi:10.1007/BF02390365

[20]   Hoffmann, S.C., Stanley, E.M., Darrin-Cox, E., et al. (2001) Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation, 72, 1444-1450. doi:10.1097/00007890-200110270-00019

[21]   Yu, A.L., Zhang, F.X., Yang, C.G., et al. (2000) Relationship between recurrent spontaneous abortion and interleukin. Chinese Journal of Practical Gynecology and Obstetrics, 4, 227-229. http://www.cnki.com.cn/Article/CJFDTotal-ZGSF200004022.htm

[22]   Berkovi?, M.C., Joki?, M., Marout, J., Radosevi?, S., et al. (2010) IL-2-330 T/G SNP and serum values-potential new tumor markers in neuroendocrine tumors of the gastrointestinal tract and pancreas (GEP-NETs). Journal of Molecular Medicine, 88, 423-429. doi:10.1007/s00109-009-0581-x

[23]   Shen, Y., Liu, Y., Liu, S., Zhang, A., et al. (2012) The association between ?330T/G polymorphism of interleukin 2 gene and bladder cancer. DNA and Cell Biology, 31, 983-987. doi:10.1089/dna.2011.1476

[24]   Chaouat, G., Menu, E., Clark, D.A., et al. (1990) Control of fetal survival in CBA × DBA/2 mice by lymphokine therapy. Journal of Reproduction & Fertility, 89, 447-457. doi:10.1530/jrf.0.0890447

[25]   Favier, R., Edelman, P., Mary, J.Y., Sadoul, G. and Douay, L. (1990) Presence of elevated serum interleukin-2 levels in pregnant women. The New England Journal of Medicine, 322, 270. doi:10.1056/NEJM199001253220413

[26]   Brunda, M.Y., Tarnowski, D. and Davatelis, V. (1986) Interaction of recombinant interferons with recombinant interleukin-2: Differential effects on natural killer cell activity and interleukin-2 activated killer ceils. International Journal of Cancer, 37, 787. doi:10.1002/ijc.2910370522