Skip to main content
SpringerLink
Log in

A functional polymorphism in the promoter region of interleukin-10 gene increases the risk for spontaneous abortions—a triad study

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Spontaneous abortion or miscarriage is the natural death of an embryo or foetus in the early stages of prenatal development. Interleukin-10 is an anti-inflammatory cytokine, produced by human cytotrophoblasts, and defects in its production result in specific pathological conditions during pregnancy. The present study is aimed to evaluate the association of IL-10 -1082G/A polymorphism in spontaneous abortions by comparing foetal, maternal and paternal groups—a triad study.

Methods

A total of 50 families with spontaneous abortions and 60 families with medically terminated pregnancies were considered for the present study. DNA from foetal tissue and parental blood samples were extracted, and the genotype analysis of IL-10 -1082G/A promoter polymorphism was carried out by amplification refractory mutation system-polymerase chain reaction followed by agarose gel electrophoresis. A statistical analysis was applied to test for the significance of the results.

Results

There was a statistically significant difference in the distribution of AA genotypes and A allele of IL-10 -1082G/A between the two family groups among foetuses (P = 0.0002) and mothers (P = 0.00005). The paternal group showed no significant difference in the genotype distribution of IL-10 between cases and controls.

Conclusion

In conclusion, IL-10 G-1082A gene promoter polymorphism may act as a major genetic regulator in the etiology of spontaneous abortions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Warburton D, Fraser FC. Spontaneous abortion risks in man: data from reproductive histories collected in a medical genetics unit. Am J Hum Genet. 1964;16:1–25.

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Coulam CB, Clark DA, Beer AE, Kutteh WH, Silver R, Kwak J. Current clinical options for diagnosis and treatment of recurrent spontaneous abortion. Am J Reprod Immunol. 1997;38:57–74.

    Article  CAS  PubMed  Google Scholar 

  3. Stray-Pedersen B, Stray-Pedersen S. Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion. Am J Obstet Gynecol. 1984;148:140–6.

    Article  CAS  PubMed  Google Scholar 

  4. Wilcox AJ, Weinberg CR, O’Connor JF, et al. Incidence of early loss of pregnancy. N Engl J Med. 1988;319:189–94.

    Article  CAS  PubMed  Google Scholar 

  5. Chard T. Frequency of implantation and early pregnancy loss in natural cycles. Baillieres Clin Obstet Gynaecol. 1991;5:179–89.

    Article  CAS  PubMed  Google Scholar 

  6. Maconochie N, Doyle P, Prior S, Simmons R. Risk factors for first trimester miscarriage—results from a UK-population-based case–control study. BJOG. 2007;114:170–86.

    Article  CAS  PubMed  Google Scholar 

  7. Rochebrochard ED, Thonneau P. Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study. Hum Reprod. 2002;17:1649–56.

    Article  PubMed  Google Scholar 

  8. Regan L, Rai R. Epidemiology and the medical causes of miscarriage. Clin Obstet Gynaecol. 2000;14:839–54.

    CAS  Google Scholar 

  9. Baxevanis CN, Gritzapis AD, Papamichail M. In vivo antitumor activity of NKT cells activated by the combination of IL-12 and IL-18. J Immunol. 2003;171:2953–9.

    Article  CAS  PubMed  Google Scholar 

  10. Conti P, Kempuraj D, Kandere K, di Gioacchino M, Barbacane RC, Castellani ML, et al. IL-10, an infiammatory/inhibitory cytokine, but not always. Immunol Lett. 2003;86:123–9.

    Article  CAS  PubMed  Google Scholar 

  11. Wakkach A, Cottrez F, Groux H. Can interleukin-10 be used as a true immunoregulatory cytokine? Eur Cytokine Netw. 2000;11:153–60.

    CAS  PubMed  Google Scholar 

  12. Chaouat G, Ledee-Bataille N, Dubanchet S, Zourbas S, Sandra O, Martal J. Reproductive immunology 2003: reassessing the TH1/TH2 paradigm. Immunol Lett. 2004;92:207–14.

    Article  CAS  PubMed  Google Scholar 

  13. Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal–fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today. 1993;14:353–6.

    Article  CAS  PubMed  Google Scholar 

  14. Lin H, Mosmann TR, Guilbert L, Tuntipopipat S, Wegmann TG. Synthesis of T helper 2-type cytokines at the maternal–fetal interface. J Immunol. 1993;151:4562–73.

    CAS  PubMed  Google Scholar 

  15. Jenkins C, Roberts J, Wilson R, MacLean MA, Shilito J, Walker J. Evidence of a th1 type response associated with recurrent miscarriage. Fertil Steril. 2000;73:1206–8.

    Article  CAS  PubMed  Google Scholar 

  16. Chaoua G, Zourbast S, Ostojic S, Lappree-delage G, Debanchet S, Ledee N, et al. A brief review on recent data on some cytokine expression at the materno-foeto interface which might challenge the classical Th1/Th2 dichotomy. J Reprod Immunol. 2002;53:241–56.

    Article  Google Scholar 

  17. Austgulen R, Lien E, Liabakk NB, Jacobsen G, Arntzen KJ. Increased levels of cytokines and cytokine activity modifiers in normal pregnancy. Eur J Obstet Gynecol Reprod Biol. 1994;57:149–55.

    Article  CAS  PubMed  Google Scholar 

  18. Blin N, Stafford DW. A general method for isolation of high molecular weight DNA from eukaryotes. Nucleic Acids Res. 1976;3:2303–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Perrey C, Turner SJ, Pravica V, Howell WM, Hutchinson IV. ARMS-PCR methodologies to determine IL-10, TNF-alpha, TNF-beta and TGF-beta 1 gene polymorphisms. Transpl Immunol. 1999;7:127–8.

    Article  CAS  PubMed  Google Scholar 

  20. Sowmya S, Aruna R, Sunitha T, Pratibha N, Jyothy A, Venkateshwari A. Evaluation of interleukin-10 (G-1082A) promoter polymorphism in preeclampsia. J Reprod Infertil. 2013;14:62–6.

    PubMed Central  PubMed  Google Scholar 

  21. Choi YK, Kwak-Kim J. Cytokine gene polymorphisms in recurrent spontaneous abortions: a comprehensive review. Am J Reprod Immunol. 2008;60:91–110.

    Article  CAS  PubMed  Google Scholar 

  22. Daher S, Shulzhenko N, Morgun A, Mattar R, Rampim GF, Camano L, et al. Associations between cytokine gene polymorphisms and recurrent pregnancy loss. J Reprod Immunol. 2003;58:69–77.

    Article  CAS  PubMed  Google Scholar 

  23. Kamali-Sarvestani E, Zolghadri J, Gharesi-Fard B, Sarvari J. Cytokine gene polymorphisms and susceptibility to recurrent pregnancy loss in Iranian women. J Reprod Immunol. 2005;65:171–8.

    Article  CAS  PubMed  Google Scholar 

  24. Babbage SJ, Arkwright PD, Vince GS, Perrey C, Pravica V, Quenby S, et al. Cytokine promoter gene polymorphisms and idiopathic recurrent pregnancy loss. J Reprod Immunol. 2001;1:21–7.

    Article  Google Scholar 

  25. Parveen F, Shukla A, Agarwal S. Cytokine gene polymorphisms in northern Indian women with recurrent miscarriages. Fertil Steril. 2013;99:433–40. doi:10.1016/j.fertnstert.2012.09.025.

    Article  CAS  PubMed  Google Scholar 

  26. Medica I, Ostojic S, Pereza N, Kastrin A, Peterlin B. Association between genetic polymorphisms in cytokine genes and recurrent miscarriage—a meta-analysis. Reprod BioMed Online. 2009;19:406–14.

    Article  CAS  PubMed  Google Scholar 

  27. Bohiltea CL M.D, Radoi VE. Interleukin-6 and interleukin-10 gene polymorphisms and recurrent pregnancy loss in Romanian population. Iran J Reprod Med. 2014;12:617–22.

    CAS  Google Scholar 

  28. Karhukorpi J, Leitinen T, Karttunen R, Tiilikainen AS. The functionally important IL-10 promoter polymorphism (-1082G A) is not a major genetic regulator in recurrent spontaneous abortions. Mol Hum Reprod. 2001;l 7:201–3.

    Article  Google Scholar 

  29. Alkhuriji AF, Alhimaidi AR, Babay ZA, Wary AS. The relationship between cytokine gene polymorphism and unexplained recurrent spontaneous abortion in Saudi females. Saudi Med J. 2013;34:484–9.

    PubMed  Google Scholar 

  30. Bahadori M, Saeed Zarei S, Zarnani AH, Zarei O, Idali F, Hadavi R, et al. IL-6, IL-10 and IL-17 gene polymorphisms in Iranian women with recurrent miscarriage. Iran J Immunol. 2014;11:97–104.

    PubMed  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Cell Biology, Institute of Genetics and Hospital for Genetic Diseases, Osmania University, Begumpet, Hyderabad, 500016, India

    M. Vidyadhari, M. Sujatha, A. Jyothy & A. Venkateshwari

  2. Government Modern Maternity Hospital, Petlaburz, Hyderabad, India

    P. Krupa

  3. Department of Genetics, Osmania University, Hyderabad, India

    Pratibha Nallari

Authors
  1. M. Vidyadhari
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Sujatha
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Krupa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Jyothy
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pratibha Nallari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Venkateshwari
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Venkateshwari.

Additional information

Capsule

This is the first case-control and family-based triad study that has analysed the association between IL-10 gene (-1082G/A) polymorphism and spontaneous abortions. The findings of the present study showed a statistically significant association of IL 10 (-1082 G/A) with spontaneously aborted foetuses and mothers and not fathers with their respective control groups. IL-10 -1082AA genotype is a foetal risk as well as maternal risk but not a paternal risk factor for spontaneous abortions. IL-10 (-1082G/A) promoter polymorphism may act as a major genetic regulator in the etiology of spontaneous abortions.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Vidyadhari, M., Sujatha, M., Krupa, P. et al. A functional polymorphism in the promoter region of interleukin-10 gene increases the risk for spontaneous abortions—a triad study. J Assist Reprod Genet 32, 1129–1134 (2015). https://doi.org/10.1007/s10815-015-0504-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-015-0504-4

Keywords

Search

Navigation