Association of folate cycle polymorphic genes with pregnancy complications in women of the Kazakh ethnic group
DOI:
https://doi.org/10.26577//eb.2020.v82.i1.09Abstract
The study of the polymorphism of folate cycle genes MTR, MTRR, MTHFR in women of the Kazakh ethnic group with complications of pregnancy (risk group, 196 pregnant women) and with the standard physiological course of pregnancy (control, 198 pregnant women) was carried out. In women at risk, the first two pregnancies ended up with spontaneous miscarriages, a pre-eclampsia, eclampsia, fetal loss syndrome, and other obstetric complications which were reported in the anamnesis. In the control group, the first two or more pregnancies completed with normal child birth; there was no history of pregnancy complications recorded in the anamnesis. The study was conducted by the case-control method. DNA isolated from venous blood leukocytes was used for PCR analysis in RealTime mode using allele-specific primers indicating gene polymorphism. A statistical analysis of the association of genetic polymorphisms was fulfilled using Software GraphPad Instat ™ Software (V. 2.04. Ralf Stahlman, Purdue University) and standard techniques. To determine the association of alleles and genotypes with pregnancy complications using the odds ratio indicator (OR, 95% CI), 4 types of inheritance models (multiplicative, total, dominant and recessive) were considered. The analysis of the association of various gene combinations of the folate cycle genes with pathology was applied. The data obtained for the frequency of occurrence of polymorphic variants of the folate cycle genes in pregnant women at risk and in the control group did not reveal statistically significant differences across all inheritance models. Also, no statistically significant differences were determined between the examined groups when analyzing the association of various variants of the studied genes with pregnancy complications. The data suggest that polymorphism of folate cycle genes does not play a significant part in the formation of the pregnancy complications in women of the Kazakh ethnic group.
Keywords: pregnancy complications, folate cycle genes, gene polymorphism.
References
2. Crider K.S., Yang T.P., Berry R.J., Bailey L.B. (2012) Folate and DNA methylation: a review of molecular mechanisms and the evidence for folate’s role. Adv Nutr., no. 3(1), pp. 21–38.
3. Fetisova I.N., Lipin M.A., Poljakov A.V. (2007) Polimorfizm genov folatnogo obmena i bolezni cheloveka [Polymorphism of folate metabolism and human disease]. Vestnik novyh medicinskih tehnologij., no.1, pp. 23–28. (In Russian)
4. Pietrzik K, Bailey L, Shane B (2010) Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin. Pharmacokinet.,vol. 49, no. 8, pp. 535–548.
5. Lucock M (2000) Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol. Genet. Metab., vol. 71, no. 1–2, pp. 121–138.
6. Dobrohotova Ju.Je., Suhih G.T., Dzhobava Je.M. (2004) Gipergomocisteinemija i geneticheskie formy trombofilii v geneze nerazvivajushhejsja beremennosti [Hyperhomocysteinemia and genetic forms of thrombophilia in the genesis of non-developing pregnancy]. Akusherstvo i ginekologija., no. 3, pp. 53-57. (In Russian)
7. Belik T.V., Derevjanchuk E.G. (2010) Issledovanie chastot polimorfnyh allelej genov folatnogo cikla u materej s jembrional'noj poterej ploda [Investigation of the frequencies of polymorphic alleles of folate cycle genes in mothers with fetal loss]. Valeologija., no. 4, pp. 31-33. (In Russian)
8. Datebase OMIM, Online Mendelian Inheritance in Man. http://www.ncbi.nlm.nih.gov/entrez
9. Fekete K, Berti C, Trovato M. (2012) Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation. Nutr. J., vol. 11, pp. 75–86.
10. De Wals P., Tairou F., Van Allen M.I. (2007) Reduction in neural-tube defects after folic acid fortification in Canada. N. Engl. J. Med., vol. 357, no. 2, pp. 135–142.
11. Blencowe H., Cousens S., Modell B. (2010) Folic acid to reduce neonatal mortality from neural tube disorders. Int. J. Epidemiol., vol. 39, no.1, pp. 110–121.
12. Kim M.W., Hong S.C., Choi J.S. (2012) Homocysteine, folate and pregnancy outcomes. J. Obstet. Gynaecol., vol. 32, no. 6, pp. 520–524.
13. Livrinova V., Lega M.H., Dimcheva A.H., Samardziski I., Isjanovska R. (2015) Factor V Leiden, Prothrombin and MTHFR Mutation in Patients with Preeclamsia, Intrauterine Growth Restriction and Placental Abruption. Open Access Maced J Med Sci., vol. 4, no.3, pp. 590-594.
14. Karata S., Aydin Y., Ocer F., Buyru A., Balci H. (2012) Hereditary thrombophilia, anti-beta 2 glycoprotein 1 IgM, and anti-annexin V antibodies in recurrent pregnancy loss. American Journal Of Reproductive Immunology., vol. 67, pp. 251-255.
15. Mamedalieva N.M., Aimbetova A.R. (2011) Gipergomocisteinemija i polimorfizm genov folatnogo obmena v geneze nerazvivajushhejsja beremennosti I trimestra [Hyperhomocysteinemia and polymorphism of folate metabolism genes in the genesis of non-developing pregnancy of the first trimester]. Reproduktivnaja medicina., no. 3-4 (08-09). pp. 69-71. (In Russian)
16. Jedrychowski W, Maugeri U (2000) Epidemiologic Methods in Studing Chronic Diseases Teachning Manual. A handbook sponsored by the International Center for Studies and research in Biomedicine in Luxembourg., pp. 245-247.
17. Incebiyik A. (2014) Prevalence of thromogenic gene mutations in women with recurrent miscarriage: a retrospective study of 1,507 patients. Obstet. Gynecol. Sci., no. 57 (6), pp. 513–517.
18. Dutra CG. (2014) Lack of association between thrombophilic gene variants and recurrent pregnancy loss. Hum. Fertil (Camb)., no.17 (2), pp. 99–105.
19. Lino FL. (2015) Thrombophilic mutations and polymorphisms, alone or in combination, and recurrent spontaneous abortion. Clin. Appl. Thromb. Hemost., no. 21 (4), pp. 365–372.
20. Hubacek JA. (2015) Association of MTHFR genetic variants C677T and A1298C on predisposition to spontaneous abortion in Slavonic population. Clin. Chim. Acta., no. 440, pp. 104–107.
21. Isaoglu U. (2014) The association between inherited thrombophilia and recurrent pregnancy loss in Turkish women. Clin. Exp. Obstet. Gynecol., no. 41 (2), pp. 177–181.
22. Yildiz G. (2012) Inherited thrombophilia with recurrent pregnancy loss in Turkish women – a real phenomenon? Ginekol. Pol., no.83 (8), pp. 598–603.
23. Settin A. (2011) Methylenetetrahydrofolatereductase gene polymorphisms in Egyptian women with unexplained recurrent pregnancy loss. Genet. Test Mol Biomarkers., no. 15 (12), pp. 887–892.
24. Kim SY. (2011) Association between MTHFR 1298A>C polymorphism and spontaneous abortion with fetal chromosomal aneuploidy. Am. J. Reprod. Immunol., vol. 66, no. 4, pp. 252-258.
25. Slezak R, Łaczmański Ł (2011) The role of 1691G>A (Leiden) mutation in Factor V gene, 20210G>A in prothrombin gene and 677C>T in MTHFR gene in etiology of early pregnancy loss. Ginekol. Pol., no.6, pp. 446-450.
26. Kobashi G., Kato E.H., Morikawa M., Shimada S., Ohta K., Fujimoto S., Minakami H., Yamada H. (2005) MTHFR C677T Polymorphism and factor V Leiden mutation are nor associated with recurrent spontaneous abortion of unexplained etiology in Japanese women. Semin Thromb Hemost., no. 31, pp. 266-271.
27. Cao Y. (2013) Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: a meta-analysis. Gene., vol. 514, no. 2, pp. 105-111.
28. Demchenko N.S. (2015) Ocenka roli polimorfizma genov folatnogo cikla i angiogeneza pri nerazvivajushhejsja beremennosti [Assessment of the role of folate cycle gene polymorphism and angiogenesis in non-developing pregnancy]. Avtoref. dis. kand. med. nauk., pp. 23. (In Russian)
29. Guo QN (2012) Association of methionine synthase reductase gene polymorphism with unexplained recurrent spontaneous abortion. Zhonghua Fu Chan Ke Za Zhi., no.10, pp. 742-746.
