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DNMT1 and DNMT3A Gene Polymorphisms and Early Pregnancy Loss


DNA methyltransferase DNMT3A and DMNT1 are required for de novo and maintenance methyltransferase activities that catalyze the establishment of methylation patterns during embryogenesis and gametogenesis. Inactivation of their genes may cause embryonic lethality. We conducted a case-control study to explore the association between DNMT3A rs7590760, DNMT1 rs2228611, and DNMT1 rs8101626 polymorphisms and early pregnancy loss susceptibility in Russian women. 100 women with early pregnancy loss (EPL) were involved and divided into two subgroups consisting of 50 women: sporadic pregnancy loss (SPL) and recurrent pregnancy loss (RPL). The control group included 56 women with full term pregnancies. Genotyping was performed using PCR-RFLP methods. GG genotype and allele G of DNMT1 rs2228611 were significantly associated with EPL and RPL, and GG genotype of DNMT1rs8101626 with EPL, SPL and RPL. Our findings have shown that women carrying GG genotype of DNMT1 rs2228611 had a higher risk of EPL and RPL (OR = 3.0, 95% CI: 1.44–6.23; OR = 3.94, 95% CI: 1.92–8.09 respectively) as well as that carrying GG genotype of DNMT1 rs8101626 are at higher risk of EPL and RPL (OR = 2.64, 95% CI: 1.2– 5.76). Conclusion: our results suggest that DNMT1 rs2228611 and DNMT1 rs8101626 gene polymorphisms are associated with early pregnancy loss and can be a genetic risk factor for recurrent pregnancy loss.

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  1. 1

    Weintraub, A.Y. and Sheiner, E., Early pregnancy loss, in Bleeding during Pregnancy: A Comprehensive Guide, Springer-Verlag, 2011, pp. 25—44.

    Google Scholar 

  2. 2

    Recurrent Pregnancy Loss. Guideline of the European Society of Human Reproduction and Embryology, 2017, pp. 1—152.

  3. 3

    El Hachem, H., Crepaux, V., May-Panloup, P., et al., Recurrent pregnancy loss: current perspective, Int. J. Womens Health, 2017, vol. 9, pp. 331—345.

    CAS  Article  Google Scholar 

  4. 4

    García-Enguídanos, A., Calle, M.E., Valero, J., et al., Risk factors in miscarriage: a review, Eur. J. Obstet., Gynecol., Reprod. Biol., 2002, vol. 102, no. 2. pp. 111—119.

    Article  Google Scholar 

  5. 5

    Bolor, H., Mori, T., Nishiyama, S., et al., Mutations of the SYCP3 gene in women with recurrent pregnancy loss, Am. J. Hum. Genet., 2009, vol. 84, no. 1, pp. 14—20.

    CAS  Article  Google Scholar 

  6. 6

    Foulk Russell, A., Implantation of the human embryo, Advances in Embryo Transfer, Bin Wu, Ed., InTech, 2012, pp. 193—206. advances-in-embryotransfer/implantation-of-the-embryo.

  7. 7

    Scott, J.R., Gibbs, R.S., Karlan, B.Y., Haney, A.F., et al., Danforth’s Obstetrics and Gynecology, Lippincott Williams and Wilkin, 2003.

    Google Scholar 

  8. 8

    Tajima, S., Suetake, I., Takeshita, K., et al., Domain structure of the Dnmt1, Dnmt3a, and Dnmt3b DNA methyltransferases, Adv. Exp. Med. Biol., 2016, vol. 945, pp. 63—86.

    CAS  Article  Google Scholar 

  9. 9

    Lyko, F., The DNA methyltransferase family: a versatile toolkit for epigenetic regulation, Nat. Rev. Genet., 2018, vol. 19, no. 2, pp. 81—92.

    CAS  Article  Google Scholar 

  10. 10

    Barišić, A., Pereza, N., Hodžić, A., et al., A single nucleotide polymorphism of DNA methyltransferase 3B gene is a risk factor for recurrent spontaneous abortion, Am. J. Reprod. Immunol., 2017, vol. 78, no. 6, pp. 1—7.

    Article  Google Scholar 

  11. 11

    Mostowska, A., Sajdak, S., Pawlik, P., et al., DNMT1, DNMT3A and DNMT3B gene variants in relation to ovarian cancer risk in the Polish population, Mol. Biol. Rep, 2013, vol. 40, no. 8, pp. 4893—4899.

    CAS  Article  Google Scholar 

  12. 12

    Xiang, G., Zhenkun, F., Shuang, C., et al., Association of DNMT1 gene polymorphisms in exons with sporadic infiltrating ductal breast carcinoma among Chinese Han women in the Heilongjiang province, Clin. Breast Cancer, 2010, vol. 10, no. 5, pp. 373—377.

    Article  Google Scholar 

  13. 13

    Kelemen, L.E., Sellers, T.A., Schildkraut, J.M., et al., Genetic variation in the one-carbon transfer pathway and ovarian cancer risk, Cancer Res., 2008, vol. 68, no. 7, pp. 2498—2506.

    CAS  Article  Google Scholar 

  14. 14

    Sun, M.Y., Yang, X.X., Xu, W.W., et al., Association of DNMT1 and DNMT3B polymorphisms with breast cancer risk in Han Chinese women from South China, Genet. Mol. Res., 2012, vol. 11, no. 4, pp. 4330—4341.

    CAS  Article  Google Scholar 

  15. 15

    Cheng, P., Chen, H., Zhang, R.P., et al., Polymorphism in DNMT1 may modify the susceptibility to oligospermia, Reprod. Biomed. Online, 2014, vol. 28, no. 5, pp. 644—649.

    CAS  Article  Google Scholar 

  16. 16

    Li, E., Chromatin modification and epigenetic reprogramming in mammalian development, Nat. Rev. Genet., 2002, vol. 3, no. 9, pp. 662—673.

    CAS  Article  Google Scholar 

  17. 17

    Okano, M., Bell, D.W., Haber, D.A., et al., DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development, Cell, 1999, vol. 99, no. 3, pp. 247—257.

    CAS  Article  Google Scholar 

  18. 18

    Gaudet, F., Rideout, W.M., Meissner, A., et al., Dnmt1 expression in pre- and postimplantation embryogenesis and the maintenance of IAP silencing, Mol. Cell Biol., 2004, vol. 24, no. 4, pp. 1640—1648.

    CAS  Article  Google Scholar 

  19. 19

    Li, E., Bestor, T.H., and Jaenisch, R., Targeted mutation of the DNA methyltransferase gene results in embryonic lethality, Cell, 1992, vol. 69, no. 6, pp. 915—926.

    CAS  Article  Google Scholar 

  20. 20

    Jia, Z., Wu, X., Cao, D., et al., Polymorphisms of the DNA methyltransferase 1 gene predict survival of gastric cancer patients receiving tumorectomy, Dis. Markers, 2016, 2016: 8578064.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21

    Saradalekshmi, K.R., Neetha, N.V., Sathyan, S., et al., DNA methyl transferase (DNMT) gene polymorphisms could be a primary event in epigenetic susceptibility to schizophrenia, PLoS One, 2014, vol. 9, no. 5. e98182

    Article  Google Scholar 

  22. 22

    Leng, S., Stidley, C.A., Bernauer, A.M., et al., Haplotypes of DNMT1 and DNMT3B are associated with mutagen sensitivity induced by benzo[a]pyrenediol epoxide among smokers, Carcinogenesis, 2008, vol. 29, no. 7, pp. 1380—1385.

    CAS  Article  Google Scholar 

  23. 23

    Kanai, Y., Ushijima, S., Nakanishi, Y., et al., Mutation of the DNA methyltransferase (DNMT) 1 gene in human colorectal cancers, Cancer Lett., 2003, vol. 192, no. 1, pp. 75—82.

    CAS  Article  Google Scholar 

  24. 24

    Yang, S.M., Huang, C.Y., Shiue, H.S., et al., Combined effects of DNA methyltransferase 1 and 3A polymorphisms and urinary total arsenic levels on the risk for clear cell renal cell carcinoma, Toxicol. Appl. Pharmacol., 2016, vol. 305, pp. 103—110.

    CAS  Article  Google Scholar 

  25. 25

    Yin, L.J., Zhang, Y., Lv, P.P., et al., Insufficient maintenance DNA methylation is associated with abnormal embryonic development, BMC Med., 2012, vol. 10, no. 26.

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Correspondence to M. M. Azova.

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Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the Local Ethics Committee of the Institute of Medicine of RUDN University and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all women involved in the study.

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Ahmed, A.A., Azova, M.M., Ramazanova, F.U. et al. DNMT1 and DNMT3A Gene Polymorphisms and Early Pregnancy Loss. Russ J Genet 56, 379–382 (2020).

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  • early pregnancy loss
  • recurrent pregnancy loss
  • DNMT1
  • DNMT3A