Genetic factors in the development of recurrent miscarriage: An overview of the data of meta-analyses
Objective. The review highlights the issues associated with a study of the role of genetic components in recurrent miscarriage (RM) susceptibility through generalized quantitative analysis of data.Trifonova E.A., Ganzha O.A., Gabidulina T.V., Devyatyarova L.L., Sotnikova L.S., Stepanov V.A.
Material and methods. The review includes the results of foreign and Russian meta-analyses published in the past 10 years and found in the Pubmed database on this topic.
Results. The data obtained from the meta-analyses of studies of an association of allelic variants of candidate genes with RM were generalized and the functional significance of a number of associated polymorphic markers was characterized. Consideration of the ethnicity of individuals was shown to be important in studying the role of genetic factors in the development of this disease, as well as gene-gene and gene-environmental interactions.
Conclusion. Creation of a future database including the results of associative studies with a detailed description of their design (detailed clinical characteristics of the examinees; criteria for group formations; patient ethnicity) will provide statistically significant evidence for the role of genetic components in the structure of RM susceptibility.
Keywords
recurrent miscarriage
polymorphic variant
gene
hereditary predisposition
meta-analysis
References
1. Sidelnikova V.M., Sukhikh G.T. Unintention of pregnancy. Moscow: GEOTAR-Media; 2010. 534p. (in Russian)
2. Radzinsky V.E., Solovyova A.V., Olenev A.S. Unintention of pregnancy. What in the future? Reproductive medicine. 2014; 3-4: 8-10. (in Russian)
3. Rull K., Nagirnaja L., Laan M. Genetics of recurrent miscarriage: challenges, current knowledge, future directions. Front. Genet. 2012; 3: 34.
4. Sergi C., Al Jishi T., Walker M. Factor V Leiden mutation in women with early recurrent pregnancy loss: a meta-analysis and systematic review of the causal association. Arch. Gynecol. Obstet. 2015; 291(3): 671-9. doi: 10.1007/s00404-014-3443-x.
5. Kolte A.M., Nielsen H.S., Steffensen R., Crespi B., Christiansen O.B. Inheritance of the 8.1 ancestral haplotype in recurrent pregnancy loss. Evol. Med. Public Health. 2015; (1): 325-31. doi: 10.1093/emph/eov031.
6. Schulze R. Meta-analysis: a comparision of approaches. Cambridge, MA: Hogrefe & Huber; 2004. 242p.
7. Nair R.R., Khanna A., Singh K. Association of GSTT1 and GSTM1 polymorphisms with early pregnancy loss in an Indian population and a meta-analysis. Reprod. Biomed. Online. 2013; 26(4): 313-22. doi: 10.1016/j.rbmo.2012.12.004.
8. Ren A., Wang J. Methylenetetrahydrofolate reductase C677T polymorphism and the risk of unexplained recurrent pregnancy loss: a meta-analysis. Fertil. Steril. 2006; 86(6): 1716-22. doi: 10.1016/j.fertnstert.2006.05.052.
9. Cao Y., Xu J., Zhang Z., Huang X., Zhang A., Wang J. et al. Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: a meta-analysis. Gene. 2013; 514(2): 105-11. doi: 10.1016/j.gene.2012.10.091.
10. Chen H., Yang X., Lu M. Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis. Arch. Gynecol. Obstet. 2016; 293(2): 283-90. doi: 10.1007/s00404-015-3894-8.
11. Nair R.R., Khanna A., Singh R., Singh K. Association of maternal and fetal MTHFR A1298C polymorphism with the risk of pregnancy loss: a study of an Indian population and a meta-analysis. Fertil. Steril. 2013; 99(5): 1311-8. e4. doi: 10.1016/j.fertnstert.2012.12.027.
12. Gao H., Tao F.B. Prothrombin G20210A mutation is associated with recurrent pregnancy loss: a systematic review and meta-analysis update. Thromb. Res. 2015; 135(2): 339-46. doi: 10.1016/j.thromres.2014.12.001.
13. Li J., Wu H., Chen Y., Wu H., Xu H., Li L. Genetic association between FXIII and β-fibrinogen genes and women with recurrent spontaneous abortion: a meta- analysis. J. Assist. Reprod. Genet. 2015; 32(5): 817-25. doi: 10.1007/s10815-015-0471-9.
14. Wang X., Jiang W., Zhang D. Association of 14-bp insertion/deletion polymorphism of HLA-G gene with unexplained recurrent spontaneous abortion: a meta-analysis. Tissue Antigens. 2013; 81(2): 108-15. doi: 10.1111/tan.12056.
15. Agrawal S., Parveen F., Faridi R.M., Prakash S. Interleukin-1 gene cluster variants and recurrent pregnancy loss among North Indian women: retrospective study and meta-analysis. Reprod. Biomed. Online. 2012; 24(3): 342-51. doi: 10.1016/j.rbmo.2011.11.021.
16. Nair R.R., Khanna A., Singh K. Association of interleukin 1 receptor antagonist (IL1RN) gene polymorphism with recurrent pregnancy loss risk in the North Indian Population and a meta-analysis. Mol. Biol. Rep. 2014; 41(9): 5719-27. doi: 10.1007/s11033-014-3443-8.
17. 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(3): 406-14.
18. Bombell S., McGuire W. Cytokine polymorphisms in women with recurrent pregnancy loss: meta-analysis. Aust. N. Z. J. Obstet. Gynaecol. 2008; 48(2): 147-54. doi: 10.1111/j.1479-828X.2008.00843.x.
19. Chen H., Yang X., Du J., Lu M. Interleukin-18 gene polymorphisms and risk of recurrent pregnancy loss: A systematic review and meta-analysis. J. Obstet. Gynaecol. Res. 2015; 41(10): 1506-13. doi: 10.1111/jog.12800.
20. Zhang B., Liu T., Wang Z. Association of tumor necrosis factor-α gene promoter polymorphisms (-308G/A, -238G/A) with recurrent spontaneous abortion: a meta-analysis. Hum. Immunol. 2012; 73(5): 574-9. doi: 10.1016/j.humimm.2012.01.008.
21. Li H.H., Xu X.H., Tong J., Zhang K.Y., Zhang C., Chen Z.J. Association of TNF-α genetic polymorphisms with recurrent pregnancy loss risk: a systematic review and meta-analysis. Reprod. Biol. Endocrinol. 2016; 14: 6. doi: 10.1186/s12958-016-0140-6.
22. Su M.T., Lin S.H., Chen Y.C. Association of sex hormone receptor gene polymorphisms with recurrent pregnancy loss: a systematic review and meta-analysis. Fertil. Steril. 2011; 96(6): 1435-44. e1. doi: 10.1016/j.fertnstert.2011.09.030.
23. Yang C., Fangfang W., Jie L., Yanlong Y., Jie W., Xuefei L. et al. Angiotensin-converting enzyme insertion/deletion (I/D) polymorphisms and recurrent pregnancy loss: a meta-analysis. J. Assist. Reprod. Genet. 2012; 29(11): 1167-73. doi: 10.1007/s10815-012-9870-3.
24. Wang Z., Wang P., Wang X., He X., Wang Z., Xu D. et al. Significant association between angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of recurrent miscarriage: a systematic review and meta-analysis. Metabolism. 2013; 62(9): 1227-38. doi: 10.1016/j.metabol.2013.03.003.
25. Su M.T., Lin S.H., Chen Y.C., Kuo P.L. Genetic association studies of ACE and PAI-1 genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Thromb. Haemost. 2013; 109(1): 8-15. doi: 10.1160/TH12-08-0584.
26. Pereza N., Ostojić S., Zdravčević M., Volk M., Kapović M., Peterlin B. Insertion/deletion polymorphism in intron 16 of ACE gene in idiopathic recurrent spontaneous abortion: case-control study, systematic review and meta-analysis. Reprod. Biomed. Online. 2016; 32(2): 237-46. doi: 10.1016/j.rbmo.2015.11.003.
27. Su M.T., Lin S.H., Chen Y.C. Genetic association studies of angiogenesis- and vasoconstriction-related genes in women with recurrent pregnancy loss: a systematic review and meta-analysis. Hum. Reprod. Update. 2011; 17(6): 803-12. doi: 10.1093/humupd/dmr027.
28. Cao Y., Zhang Z., Xu J., Wang J., Yuan W., Shen Y. et al. Genetic association studies of endothelial nitric oxide synthase gene polymorphisms in women with unexplained recurrent pregnancy loss: a systematic and meta-analysis. Mol. Biol. Rep. 2014; 41(6): 3981-9. doi: 10.1007/s11033-014-3266-7.
29. Pereza N., Peterlin B., Volk M., Kapović M., Ostojić S. A critical update on endothelial nitric oxide synthase gene variations in women with idiopathic recurrent spontaneous abortion: genetic association study, systematic review and meta-analyses. Mol. Hum. Reprod. 2015; 21(5): 466-78. doi: 10.1093/molehr/gav008.
30. Tang W., Zhou X., Chan Y., Wu X., Luo Y. p53 codon 72 polymorphism and recurrent pregnancy loss: a meta-analysis. J. Assist. Reprod. Genet. 2011; 28(10): 965-9. doi: 10.1007/s10815-011-9618-5.
31. Chen H., Yang X., Wang Z. Association between p53 Arg72Pro polymorphism and recurrent pregnancy loss: an updated systematic review and meta-analysis. Reprod. Biomed. Online. 2015; 31(2): 149-53. doi: 10.1016/j.rbmo.2015.05.003.
32. Chen H., Nie S., Lu M. Association between plasminogen activator inhibitor-1 gene polymorphisms and recurrent pregnancy loss: a systematic review and meta-analysis. Am. J. Reprod. Immunol. 2015; 73(4): 292-300. doi: 10.1111/aji.12321.
33. Li X., Liu Y., Zhang R., Tan J., Chen L., Liu Y. Meta-analysis of the association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss. Med. Sci. Monit. 2015; 21: 1051-6. doi: 10.12659/MSM.892898.
34. Zhang B., Dai B., Zhang X., Wang Z. Vascular endothelial growth factor and recurrent spontaneous abortion: a meta-analysis. Gene. 2012; 507(1): 1-8. doi: 10.1016/j.gene.2012.06.049.
35. Xu X., Du C., Li H., Du J., Yan X., Peng L. et al. Association of VEGF genetic polymorphisms with recurrent spontaneous abortion risk: a systematic review and meta-analysis. PLoS One. 2015; 10(4): e0123696. doi: 10.1371/journal.pone.0123696.
36. Трифонова Е.А., Габидулина Т.В., Агаркова Т.А., Габитова Н.А., Степанов В.А. Гомоцистеин, полиморфизмы гена MTHFR и осложнения беременности. Акушерство и гинекология. 2011; 2: 8-15. [Trifonova E.A., Gabidulina T.V., Agarkova T.A., Gabitova N.A., Stepanov V.A. Homocysteine, MTHFR gene polymorphisms, and pregnancy complications. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2011; (2): 8-15. (in Russian)
37. Trifonova E.A., Gabidulina T.V., Buharina I.Yu., Stepanov V.A. The role of factors of hereditary predisposition in the development of pre-eclampsia: an overview of meta-analysis data. Molekulyarnaya meditsina. 2016; 1: 8-14. (in Russian)
38. Ramón L.A., Gilabert–Estellés J., Cosín R., Gilabert J., España F., Castelló R. et al. Plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism and endometriosis. Influence of PAI-1 polymorphism on PAI-1 antigen and mRNA expression. Thromb. Res. 2008; 122(6): 854-60.
39. Serrano N.C., Díaz L.A., Páez M.C., Mesa C.M., Cifuentes R., Monterrosa A. et al. Angiotensin-converting enzyme I/D polymorphism and pre-eclampsia risk: evidence of small-study bias. PLoS Med. 2006; 3(12): e520.
40. Amirchaghmaghi E., Rezaei A., Moini A., Roghaei M.A., Hafezi M., Aflatoonian R. Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion. Cell J. 2015; 16(4): 538-45.
41. Galazios G., Papazoglou D., Tsikouras P., Kolios G. Vascular endothelial growth factor gene polymorphisms and pregnancy. J. Matern. Fetal Neonatal Med. 2009; 22(5): 371-8. doi: 10.1080/14767050802645035.
42. Su M.T., Lin S.H., Chen Y.C., Kuo P.L. Gene-gene interactions and risk of recurrent miscarriages in carriers of endocrine gland-derived vascular endothelial growth factor and prokineticin receptor polymorphisms. Fertil. Steril. 2014; 102(4): 1071-7. e3. doi: 10.1016/j.fertnstert.2014.06.042.
Received 19.08.2016
Accepted 02.09.2016
About the Authors
Trifonova Ekaterina Aleksandrovna, Candidate of Medical Science, Research Associate, Research Institute of Medical Genetics, Tomsk Research Medical Center.634050, Russia, Tomsk, Embankment of the river Ushayki, 10. Tel.: +73822513334. E-mail: ekaterina.trifonova@medgenetics.ru
Ganzha Olga Aleksandrovna, a resident of the State Public Health Service of the Siberian State Medical University, Ministry of Health of Russia.
634050, Russia, Tomsk, Moscow highway, 2. Tel.: +79234227446. E-mail: ganzha.olga42@gmail.com
Gabidulina Tatyana Vasilievna, MD, associate professor of the obstetrics and gynecology department, o Siberian State Medical University, Ministry of Health of Russia.
634050, Russia, Tomsk, Moscow highway, 2. Tel.: +79138501120. E-mail: helen556@yandex.ru
Devyatyarova Larisa Leonidovna, obstetrician-gynecologist, Regional Perinatal Center.
634049, Russia, Tomsk, Ivana Chernykh str. 96/1. Tel.: +73822644900. E-mail: dev-larisa@yandex.ru
Sotnikova Larisa Stepanovna, MD, Professor of the Department of Obstetrics and Gynecology, Siberian State Medical University, Ministry of Health of Russia.
634050, Russia, Tomsk, Moscow highway, 2. Tel.: +73822901101. E-mail: sotnikova-larisa@mail.ru
Stepanov Vadim Anatolyevich, Doctor of Biological Sciences, Professor, Director of Research Institute of Medical Genetics, Tomsk Research Medical Center.
634050, Russia, Tomsk, Embankment of the river Ushayki, 10. Tel.: +73822513334. E-mail: vadim.stepanov@medgenetics.ru
For citations: Trifonova E.A., Ganzha O.A., Gabidulina T.V., Devyatyarova L.L., Sotnikova L.S., Stepanov V.A. Genetic factors in the development of recurrent miscarriage: An overview of the data of meta-analyses. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (4): 14-20. (in Russian)
http://dx.doi.org/10.18565/aig.2017.4.14-20
Similar Articles
