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ASSOCIATION BETWEEN CYTOKINE GENE POLYMORPHISMS AND RECURRENT MISCARRIAGE

https://doi.org/10.15789/1563-0625-2017-5-585-596

Abstract

Associations between IL1B (rs1143634), IL1RN (VNTR, intron 2), IL4 (VNTR, intron 3), TNFA (rs1800629, rs361525), IL6 (rs1800795), and IL10 (rs1800896) genetic polymorphisms in women with recurrent miscarriage (RM) were analyzed. We studied DNA samples of 112 women with RM and 267 women with physiological pregnancy. The IL1RN, IL4 genotypes were identified by PCR techniques, the IL1B, IL6 gene polymorphisms were defined by means of RFLP approach. To detect TNFA and IL10 gene polymorphisms, TaqMan real-time PCR was used. The results have shown that polymorphic loci of IL1B, IL1RN, IL10, TNFA genes were not associated with RM, and early spontaneous abortion risk. The 2R allele of IL4 gene was found to be associated with higher RM risk (OR = 1.52; 95% CI = [1.08-2.14]; P-value (cor) = 0.05), and G allele of IL6 gene was associated with a risk for > 3 early spontaneous abortions (OR = 2.10; 95% CI = [1.24-3.56]; P-value (cor) = 0.05), in an additive inheritance model. Upon evaluation of the data obtained, one may conclude that the IL4 (VNTR intron 3) and IL6 (rs1800795) gene polymorphisms could influence the RM development. These results may be useful for assessment of molecular mechanisms underlying early spontaneous abortion.

About the Authors

L A. Gordeeva
Federal Research Center of Coal and Coal Chemistry (Institute of Human Ecology, Siberian Branch, Russian Academy of Sciences)
Russian Federation

Gordeeva L.A., PhD (Biology), Head, Laboratory of Immunogenetics, Federal Research Center of Coal and Coal Chemistry (Institute of Human Ecology, Siberian Branch, Russian Academy of Sciences).

Kemerovo.



O. S. Oskorbina
Federal Research Center of Coal and Coal Chemistry (Institute of Human Ecology, Siberian Branch, Russian Academy of Sciences).
Russian Federation

Oskorbina O.S., Leading Engineer-biologist, Laboratory of Immunogenetics, Federal Research Center of Coal and Coal Chemistry (Institute of Human Ecology, Siberian Branch, Russian Academy of Sciences).

Kemerovo.



E. N. Voronina
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences.
Russian Federation

Voronina E.N., PhD (Biology), Research Associate, Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences.

Novosibirsk.



E. A. Sokolova
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences.
Russian Federation

Sokolova E.A., PhD (Biology), Engineer, Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy  of Sciences.

Novosibirsk.



I. V. Shatalina
Federal Research Center of Coal and Coal Chemistry (Institute of Human Ecology, Siberian Branch, Russian Academy of Sciences).
Russian Federation

Shatalina I.V., Leading Engineer-biologist, Laboratory of Immunogenetics, Federal Research Center of Coal and Coal Chemistry (Institute of Human Ecology, Siberian Branch, Russian Academy of Sciences).

Kemerovo.



R. V. Olennikova
Kemerovo Regional Clinical Hospital, Genetic Consulting Center.
Russian Federation

Olennikova R.V., Clinical Geneticist, Kemerovo Regional Clinical Hospital, Genetic Consulting Center.

Kemerovo.



S. L. Nersesyan
Kemerovo Regional Clinical Hospital, Genetic Consulting Center.
Russian Federation

Nersesyan S.L., Clinical Geneticist, Kemerovo Regional Clinical Hospital, Genetic Consulting Center.

Kemerovo.



M. L. Filipenko
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences.
Russian Federation

Filipenko M.L., PhD (Biology), Head, Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy  of Sciences.

Novosibirsk.



A. N. Glushkov
Federal Research Center of Coal and Coal Chemistry (Institute of Human Ecology, Siberian Branch, Russian Academy of Sciences).
Russian Federation

Glushkov A.N., PhD, MD (Medicine), Deputy Director, The Federal Research Center of Coal and Coal Chemistry (Institute of Human Ecology, Siberian Branch, Russian Academy of Sciences).

Kemerovo.



References

1. Александрова Н.В., Донников А.Е. Использование современных ДНК-технологий в прогнозировании акушерских осложнений при беременности высокого риска // Мать и дитя в Кузбассе, 2012. Т. 48, № 1. С. 42-47. [Alexandrova N.V., Donnikov A.E. Prognostic tool of current DNA-technologies in obstetric complications in high risk pregnancy. Mat’ i ditya v Kuzbasse = Mother and Child in Kuzbass, 2012, Vol. 48, no. 1, pp. 42-47. (In Russ.)]

2. Гестагены у женщин разного возраста. Доказательные данные и клинический опыт. Научные материалы Общероссийского научно-практического семинара «Репродуктивный потенциал России: сибирские чтения». М.: Редакция журнала StatusPraesens, 2012. 24 с. [Gestagens in women of different ages. Evidence data and clinical experience. Research Materials of Russian scientific-practical seminar "The reproductive potential of Russia: Siberian read"]. Moscow: StatusPraesens, 2012. 24 p.

3. Гордеева Л.А., Глушкова О.А, Воронина Е.Н., Шаталина И.В., Шутров А.Е., Попова О.С., Гареева Ю.В., Симонова Т.А., Сутулина И.М., Филипенко М.Л., Глушков А.Н. Ассоциации материнских полиморфизмов генов цитокинов (IL-1B, IL-1RN, TNF, IL-4, IL-6) с врожденными пороками развития у плода и новорожденного // Иммунология, 2013. Т. 34, № 6. С. 298-304. [Gordeeva L.A., Glushkova O.A., Voronina E.N., Shatalina I.V., Shutrov A.E., Popova O.S., Gareeva Yu.V., Simonova T.A., Sutulina I.M., Filipenko M.L., Glushkov A.N. Association of maternal polymorphisms of cytokine gene (IL1B, IL1RN, TNF, IL4, IL6) with congenital malformations in fetus and newborn. Immunologiya = Immunology, 2013, Vol. 34, no. 6, pp. 298-304. (In Russ.)]

4. Данилко К.В., Корытина Г.Ф., Ахмадишина Л.З., Янбаева Д.Г., Загидуллин Ш.З., Викторова Т.В. Ассоциация полиморфных маркеров генов цитокинов (IL1B, IL1RN, TNFA, LTA, IL6, IL8, IL10) с развитием хронической обструктивной болезни легких // Молекулярная биология, 2007. Т. 41, № 1. С. 26-36. [Danilko K.V., Korytina G.F., Akhmadishina L.Z., Yanbaeva D.G., Zagidullin Sh.Z., Victorova T.V. Association of cytokines genes (IL1, IL1RN, TNF, LTA, IL6, IL8, IL10) polymorphic markers with chronic obstructive pulmonary disease. Molekulyarnaya biologiya = Molecular Biology, 2007, Vol. 41, no. 1, pp. 26-36. (In Russ.)]

5. Заморина С.А., Ширшев С.В. Хорионический гонадотропин – фактор индукции иммунной толерантности при беременности // Иммунология, 2013. Т. 34, № 2. С. 105-107. [Zamorina S.A., Shirshev S.V. Human chorionic gonadotropin is a factor in the induction of immune tolerance in pregnancy. Immunologiya = Immunology, 2013, Vol. 34, no. 2, pp. 105-107. (In Russ.)]

6. Машкина Е.В., Коваленко К.А., Фомина Н.В., Шкурат Т.П. Исследование ассоциации полиморфных вариантов генов цитокинов с ранними эмбриональными потерями // Экологическая генетика, 2014. Т. XII, № 1. С. 19-27. [Mashkina E.V., Kovalenko K.A., Fomina N.V., Shkurat T.P. Cytokine gene polymorphisms and early pregnancy loss. Ekologicheskaya genetika = Ecological Genetics, 2014, Vol. XII, no. 1, pp. 19-27. (In Russ.)]

7. Питиримова Л.Н. Загороднева Е.А. Гумилевский Б.Ю. Особенности аллельного полиморфизма генов интерлейкинов и цитокиновый баланс женщин с невынашиванием беременности // Акушерство и гинекология, 2014. № 3. С. 33-38. [Pitirimova L.N., Zagorodneva E.A., Gumilevskiy B.U. Specific features of allelic polymorphism of the interleukin genes and the cytokine balance in women with miscarriage. Akusherstvo i ginekologiya = Obstetrics and Gynecology, 2014, no. 3, pp. 33-38. (In Russ.)]

8. Рубанович А.В., Хромов-Борисов Н.Н. Теоретический анализ показателей предсказательной эффективности бинарных генетических тестов // Экологическая генетика, 2013. Т. XI, № 1. С. 77-90. [Rubanovich A.V., Khromov-Borisov N.N. Theoretical analysis of the predictability indices of the binary genetic tests. Ekologicheskaya genetika = Ecological Genetics, 2013, Vol. XI, no. 1, pp. 77-90. (In Russ.)]

9. Сидельникова В.М. Невынашивание беременности – современный взгляд на проблему // Российский вестник акушера-гинеколога, 2007. № 2. С. 62-64. [Sidelnikova V.M. Miscarriage: the present view of the problem. Rossiyskiy vestnik akushera-ginekologa = Russian Bulletin Obstetrician-Gynecologist, 2007, no. 2, pp. 62-64. (In Russ.)]

10. Симбирцев А.С. Цитокины в патогенезе инфекционных и неинфекционных заболеваний человека // Медицинский академический журнал, 2013. Т. 13, № 3. С. 18-41. [Simbirtsev A.S. Cytokines in the pathogenesis of infectious and noninfectious human diseases. Meditsinskiy akademicheskiy zhurnal = Medical Academic Journal, 2013, Vol. 13, no. 3, pp. 18-41. (In Russ.)]

11. Cухих Г.Т., Ванько Л.В. Иммунные факторы в этиологии и патогенезе осложнений беременности // Акушерство и гинекология, 2012. № 1. С. 128-136. [Sukhikh G.T., Vanko K.V. Immune factors in the etiology and pathogenesis of pregnancy complications. Akusherstvo i ginekologiya = Obstetrics and Gynecology, 2012, no. 1, pp. 128-136. (In Russ.)]

12. Фрейдлин И.С. Иммунная система и ее дефекты. СПб.: Полисан, 1998. 113 с. [Freidlin I.S. The immune system and its defects]. St. Petersburg: Polysan, 1998. 113 p.

13. Чистякова Г.Н., Газиева И.А., Ремизова И.И., Черданцева Г.А. Оценка продукции цитокинов при беременности, осложненной угрозой прерывания в первом триместре // Фундаментальные исследования, 2005. № 5. С. 96-98. [Chistyakova G.N., Gaziyeva I.A., Remizova I.I., Cherdantseva G.A. The evaluation of cytokines production by the threatened abortion in first trimester of pregnancy. Fundamental’nye issledovaniya = Fundamental Research, 2005, no. 5, pp. 96-98. (In Russ.)]

14. Шабалдин А.В., Гордеева Л.А., Глушкова О.А., Макарченко О.С., Шаталина И.В., Симонова Т.А., Филипенко М.Л., Глушков А.Н., Крюков П.М. Ассоциации сочетаний генов HLA DRB1*, IL4*, IL6* с репродуктивными потерями у женщин // Иммунология, 2008. Т. 29, № 3. С. 132-136. [Shabaldin A.V, Gordeeva L.A., Glushkova O.A., Makarchenko O.S., Shatalina I.V., Simonova T.A., Filipenko M.L., Glushkov A.N., Kryukov P.M. The association of HLA DRB1*, IL-4*, IL-6* gene combination with women’s reproductive losses. Immunologiya = Immunology, 2008, Vol. 29, no. 3, pp. 132-136. (In Russ.)]

15. Шевченко А.В., Голованова О.В., Коломейчук М.Ю., Коненков В.И., Гарбуков Е.Ю., Стахеева М.Н. Полиморфизм промоторного региона генов IL-4, IL-6 И IL-10 у пациенток с раком молочной железы // Медицинская иммунология, 2009. Т. 11, № 1. С. 21-28. [Shevchenko A.V., Golovanova O.V., Kolomejtchuk M.Yu., Konenkov V.I., Garbukov E.Yu., Stakheeva M.N. Promotor polymorphism of IL-4, IL-6, and IL-10 genes among patients with breast cancer. Meditsinskaya immunologiya = Medical Immunology, 2009, Vol. 11, no. 1, pp. 21-28. (In Russ.)]. doi: dx.doi.org/10.15789/1563-0625-2009-1-21-28.

16. Ширшев С.В. Механизмы иммунноэндокринного контроля процессов репродукции. Екатеринбург: УрО РАН, 2002, Т. 2, С. 382-392. [Shirshev S.V. Mechanisms of immune and endocrine control of reproduction processes]. Ekaterinburg: UrB RAS, 2002, Vol. 2, pp. 382-392.

17. Bahadori M., Zarei S., Zarnani A.H., Zarei O., Idali F., Hadavi R., Jeddi-Tehrani M. IL-6, IL-10 and IL-17 gene polymorphisms in Iranian women with recurrent miscarriage. Iran J. Immunol., 2014, Vol. 11, no. 2, pp. 97-104.

18. Bhayal A.C., Krishnaveni D., Rao K.P., Kumar A.R., Jyothy A.,Nallari P., Venkateshwari A. Significant Association of Interleukin4 Intron 3 VNTR Polymorphism with Susceptibility to Gastric Cancer in a South Indian Population from Telangana. PLoS One, 2015, Vol. 10, no. 9, e0138442. doi: 10.1371/journal.pone.0138442.

19. Bombell S., McGuire W. Cytokine polymorphisms in women with recurrent pregnancy loss: meta-analysis. Aust. N. Z. J. Obstet. Gynaecol., 2008, Vol. 48, no. 2, pp. 147-154.

20. Cabantous S., Poudiougou B., Oumar A.A., Traore A., Barry A., Vitte J., Bongrand P., Marquet S., Doumbo O., Dessein A.J. Genetic evidence for the aggravation of Plasmodium falciparum malaria by interleukin 4. J. Infect. Dis., 2009, Vol. 200, no. 10, pp. 1530-1539.

21. Crider K.S., Whitehead N., Buus R.M. Genetic variation associated with preterm birth: a HuGE review. Genet. Med., 2005, Vol. 7, no. 9, pp. 593-604.

22. Duan Y., Pan C., Shi J., Chen H., Zhang S. Association between interleukin-4 gene intron3 VNTR polymorphism and cancer risk. Cancer Cell Int., 2014, Vol. 14, no. 1, p. 131.

23. Fraser R., Walker J.J., Ekbote U.V., Martin K.L., McShane P., Orsi N.M. Interleukin-4 -590 (C > T), toll-like receptor-2 +2258 (G > A) and matrix metalloproteinase-9 -1562 (C > T) polymorphisms in pre-eclampsia. BJOG, 2008, Vol. 115, no. 8, pp. 1052-1056.

24. Guo R., Zheng Y., Yang J., Zheng N. Association of TNF-alpha, IL-6 and IL-1beta gene polymorphisms with polycystic ovary syndrome: a meta-analysis. BMC Genet., 2015, Vol. 16, p. 5.

25. Inanir A., Tural S., Yigit S., Kalkan G., Pancar G.S., Demir H.D., Ates O. Association of IL-4 gene VNTR variant with deep venous thrombosis in Behest’s disease and its effect on ocular involvement. Mol. Vis., 2013, no. 19, pp. 675-683.

26. Kang L., Chen C.H., Yu C.H., Chang C.H., Chang F.M. An association study of interleukin-4 gene and preeclampsia in Taiwan. Taiwan J. Obstet. Gynecol., 2014, Vol. 53, no. 2, pp. 215-219.

27. Kucherenko A.M., Vorobiova I.I., Rudakova N.V., Livshits L.A. The role of IL6 and ESR1 gene polymorphisms as immunological factors of pregnancy maintenance. Biopolymers and Cell, 2013, Vol. 29, no. 5, pp. 402-405.

28. Liu R.X., Wang Y., Wen L.H. Relationship between cytokine gene polymorphisms and recurrent spontaneous abortion. Int. J. Clin. Exp. Med., 2015, Vol. 8, no. 6, pp. 9786-9792.

29. Mohammadoo-Khorasani M., Salimi S., Tabatabai E., Sandoughi M., Zakeri Z., Farajian-Mashhadi F. Interleukin-1β (IL-1β) and IL-4 gene polymorphisms in patients with systemic lupus erythematosus (SLE) and their association with susceptibility to SLE. Indian J. Med. Res., 2016, Vol. 143, no. 5, pp. 591-596.

30. Nakashima H., Miyake K., Inoue Y., Shimizu S., Akahoshi M., Tanaka Y., Otsuka T., Harada M. Association between IL-4 genotype and IL-4 production in the Japanese population. Genes Immun., 2002, Vol. 3, no. 2, pp. 107-109.

31. Olenscki Gilli S.C., Pericole F.V., Benites B.D., Sippert E.Â., Castilho L.M., Addas-Carvalho M., Olalla Saad S.T. Cytokine polymorphisms in sickle cell disease and the relationship with cytokine expression. Exp. Hematol., 2016, Vol. 44, no. 7, pp. 583-589.

32. Parveen F., Shukla A., Agarwal S. Cytokine gene polymorphisms in northern Indian women with recurrent miscarriages. Fertil Steril., 2013, Vol. 99, no. 2, pp. 433-440.

33. Pluchino N., Drakopoulos P., Wenger J.M., Petignat P., Streuli I., Genazzani A.R. Hormonal causes of recurrent pregnancy loss (RPL). Hormones, 2014, Vol. 13, no. 3, pp. 314-322.

34. Reiman M., Kujari H., Ekholm E., Lapinleimu H., Lehtonen L., Haataja L. PIPARI Study Group. Interleukin-6 polymorphism is associated with chorioamnionitis and neonatal infections in preterm infants. J. Pediatr., 2008, Vol. 153, no. 1, pp. 19-24.

35. Resch B., Radinger A., Mannhalter C., Horvath B., Binder A., Zenz W., Walcher W., Haas J., Müller W.D., Pertl B. Maternal interleukin-6 (-174) C/C polymorphism is associated with chorioamnionitis and cysticperiventricular leucomalacia of the preterm infant. J. Perinatol., 2010, Vol. 30, no. 11, pp. 712-716.

36. Saijo Y., Sata F., Yamada H., Konodo T., Kato E.H., Kataoka S., Shimada S., Morikawa M., Minakami H., Kishi R. Interleukin-4 gene polymorphism is not involved in the risk of recurrent pregnancy loss. Am. J. Reprod. Immunol., 2004, Vol. 52, no. 2, pp. 143-146.

37. Saito S., Nakashima A., Shima T., Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am. J. Reprod. Immunol., 2010, Vol. 63, no. 6, pp. 601-610.

38. Salimi S., Mohammadoo-Khorasani M., Yaghmaei M., Mokhtari M., Moossavi M3. Possible association of IL-4 VNTR polymorphism with susceptibility to preeclampsia. Biomed Res Int., 2014, 497031. doi: 10.1155/2014/497031.

39. Sobti R.C., Berhane N., Mahdi S.A., Takur H., Wanch A. Association of interleukin 4 VNTR polymorphism and HIV/AIDS in a north Indian seropositive patients. Mol. Biol. Rep., 2012, Vol. 39, no. 3, pp. 3251-3257.

40. Unfried G., Böcskör S., Endler G., Nagele F., Huber J.C., Tempfer C.B. A polymorphism of the interleukin-6 gene promoter and idiopathic recurrent miscarriage. Hum. Reprod., 2003, Vol. 18, no. 2, pp. 267-270.

41. Vasudevan R., Norhasniza M.N., Patimah I. Association of variable number of tandem repeats polymorphism in the IL-4 gene with end-stage renaldisease in Malaysian patients. Genet. Mol. Res., 2011, Vol. 10, no. 2, pp. 943-947.

42. Villuendas G., San Millán J.L., Sancho J., Escobar-Morreale H.F. The -597 G-- > A and -174 G-- > C polymorphisms in the promoter of the IL-6 gene are associated with hyperandrogenism. J. Clin. Endocrinol. Metab., 2002, Vol. 87, no. 3, pp. 1134-1141.

43. von Linsingen R., Bompeixe E.P., Bicalho Mda G. A case-control study in IL6 and TGFB1 gene polymorphisms and recurrent spontaneous abortion in southern Brazilian patients. Am. J. Reprod. Immunol., 2005, Vol. 53, no. 2, pp. 94-99.

44. Wu W., Clark E.A., Stoddard G.J., Watkins W.S., Esplin M.S., Manuck T.A., Xing J., Varner M.W., Jorde L.B. Effect of interleukin-6 polymorphism on risk of preterm birth within population strata: a meta-analysis. BMC Genet., 2013, Vol. 14, p. 30.


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Gordeeva L.A., Oskorbina O.S., Voronina E.N., Sokolova E.A., Shatalina I.V., Olennikova R.V., Nersesyan S.L., Filipenko M.L., Glushkov A.N. ASSOCIATION BETWEEN CYTOKINE GENE POLYMORPHISMS AND RECURRENT MISCARRIAGE. Medical Immunology (Russia). 2017;19(5):585-596. (In Russ.) https://doi.org/10.15789/1563-0625-2017-5-585-596

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