Role of gene polymorphism of IL-4 and IL-17 in recurrent miscarriage, came in art cycles


  • K. P. Golovatyuk Odessa National Medical University, chief medical officer of LLC; Medical Center of Reproductive Health Protection “Gamete”, Odesa, Ukraine



assisted reproductive technology, recurrent miscarriage, typing of cytokine genes, IL-4, IL-4R, IL-17A, IL-17F, gene polymorphism


Most researchers suggest that more than 50% of pregnant women after use of assisted reproductive technologies (ART) are faced with the problem of miscarriage, especially in the first trimester.

The aim of the study was to investigate the frequency of genotypes and allelic variants of the IL-4 (S589T and S33T), IL-4R (Q576R), IL-17A (G197A) and IL-17F (488T/C) genes, depending on the reproductive status and assessment of their association with recurrent miscarriage, which occurred in ART cycles.

Peripheral blood of 240 patients – the eastern Slav with habitual miscarriage, came in ART cycles, and 100 apparently healthy fertile women in the control group with a history of at least one term delivery and lack of spontaneous abortion episodes was studied. The groups were representative of age.

DNA for molecular genetic studies of nuclei isolated from peripheral blood lymphocytes. The method is based on the destruction of lymphocytes using lysis buffer without affecting the integrity of the membranes of lymphocytes nuclei. For typing single nucleotide polymorphisms of IL-4 immune response, IL-4R, IL-17A and IL-17F using polymerase chain reaction product with the melting reaction in the presence of “adjacent” oligonucleotides.

It was found that the genotype CT-33 (OR 3.99; 95% CI 2,42–6,57) and CT-589 (OR 3.99; 95% CI 2,42–6,57) gene IL-4; genotype GG576 (OR 5.95; 95% CI 1,39–25,58) gene IL-4R and TT488 genotype (OR 2.33; 95% CI 1,39–3,91) and CC488 (OR 2.27; 95% CI 0,76–6,84) IL-17F gene were associated with a significant increase in the risk of miscarriage. On the other hand, no significant differences were found between the control group and the basic frequency of polymorphisms IL-17A-G197A (rs227593).

The results of the molecular-genetic typing it possible to identify in the Eastern Slavic population of residents of Odesa region of Ukraine immunogenetic markers of susceptibility/ resistance to the development of recurrent miscarriage. It is shown that cytokine gene typing can be used as a method of early diagnosis and pregravid prognosis of immune forms of reproductive loss in women.

Author Biography

K. P. Golovatyuk, Odessa National Medical University, chief medical officer of LLC; Medical Center of Reproductive Health Protection “Gamete”, Odesa

PhD, assistant at the department of reconstructive and regenerative medicine with reproductology course


  1. Rull, K., Nagirnaja, L., Laan, M. “Genetics of recurrent miscarriage: challenges, current knowledge, future directions.” Front Genet 3 (2012): 34. DOI: 10.3389/fgene.2012.00034
  2. Xu, X., Du, C., Li, H., et al. “Association of VEGF Genetic Polymorphisms with Recurrent Spontaneous Abortion Risk: A Systematic Review and Meta-Analysis.” PLoS One 10 (2015). DOI: 10.1371/journal.pone.0123696
  3. Guerin, L.R., Prins, J.R., Robertson, S.A. “Regulatory T-cells and immune tolerance in pregnancy: a new target for infertility treatment?” Hum Reprod Update 15 (2009): 517–35.
  4. Munoz-Suano, A., Hamilton, A.B., Betz, A.G., et al. “The immune system during pregnancy.” Immunol Rev 241 (2011): 20–38.
  5. Robertson, S.A. “Immune regulation of conception and embryo implantation-all about quality control?” J Reprod Immunol 85 (2010): 51–57.
  6. Saini, V., Arora, S., Yadav, A., et al. “Cytokines in recurrent pregnancy loss.” Clin Chim Acta 412.9–10 (2011): 702–8. DOI: 10.1016/j.cca.2011.01.002
  7. Alkhuriji, A.F., Alhimaidi, A.R., Babay, Z.A., et al. “The relationship between cytokine gene polymorphism and unexplained recurrent spontaneous abortion in Saudi females.” Saudi Medical Journal 34 (2013): 484–9.
  8. Prins, J.R., Gomez-Lopez, N., Robertson, S.A. “Interleukin-6 in pregnancy and gestational disorders.” J Reprod Immunol 95 (2012): 1–14.
  9. Bettelli, E., Carrier, Y., Gao, W., et al. “Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells.” Nature 441.7090 (2006): 235–8. DOI: 10.1038/nature04753
  10. Lombardelli, L., Logiodice, F., Aguerre-Girr, M.O., et al. “Interleukin-17-producing decidual CD4+ T cells are not deleterious for human pregnancy when they also produce interleukin-4.” Clin Mol Allergy 14 (2016): 1. DOI: 10.1186/s12948-016-0039-y
  11. Rasti, Z., Nasiri, M., Kohan, L. “The IL-6 -634C/G polymorphism: a candidate genetic marker for the prediction of idiopathic recurrentpregnancy loss.” J Reprod Biomed (Yazd) 14.2 (2016): 103–8.
  12. Luzina, I.G., Keegan, A.D., Heller, N.M., et al. “Regulation of inflammation by interleukin-4: a review of “alternatives.” J Leukoc Biol 92.4 (2012): 753–64. DOI: 10.1189/jlb.0412214
  13. Andreichikova, E.A., Piskunov, A.A., Sennikov, S.V., et al. “Comparative aspects of allelic polymorphism of IL-4 in the indigenous and alien residents of the Republic of Khakassia, patients with allergic asthma.” Bulletin SB RAMS 6.31 (2011): 69–72.
  14. Afzali, B., Lombardi, G., Lechler, R., et al. “The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease.” Clin Exp Immunol 148.1 (2007): 32–46. DOI: 10.1111/j.1365-2249.2007.03356.x
  15. Saijo, Y., Sata, F., Yamada, H., et al. “Interleukin-4 gene polymorphism is not involved in the risk of recurrent pregnancy loss.” Am J Reprod Immunol 52.2 (2004): 143–6.
  16. Tavasolian, F., Abdollahi, E., Samadi, M. “Association of the IL4R single-nucleotide polymorphism I50V with recurrent spontaneous abortion (RSA)”. J Assist Reprod Genet 31.7 (2014): 851–856. DOI: 10.1007/s10815-014-0234-z
  17. Escamilla-Tilch, M., Estrada-García, I., Granados, J., et al. “Lack of Association of the Polymorphisms IL-17A (-197G/A) and IL-17F (+7488A/G) with Multibacillary Leprosy in Mexican Patients.” International Journal of Genomics Volume 5 (2014). DOI: 10.1155/2014/920491



How to Cite

Golovatyuk, K. P. (2017). Role of gene polymorphism of IL-4 and IL-17 in recurrent miscarriage, came in art cycles. REPRODUCTIVE ENDOCRINOLOGY, (33), 26–31.