<?xml version='1.0' encoding='utf-8'?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd">
<article article-type="research-article" dtd-version="1.2" xml:lang="ru" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><front><journal-meta><journal-id journal-id-type="issn">2658-6533</journal-id><journal-title-group><journal-title>Research Results in Biomedicine</journal-title></journal-title-group><issn pub-type="epub">2658-6533</issn></journal-meta><article-meta><article-id pub-id-type="doi">10.18413/2658-6533-2020-6-1-0-4</article-id><article-id pub-id-type="publisher-id">1961</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genetics</subject></subj-group></article-categories><title-group><article-title>&lt;strong&gt;The study of the association of polymorphic loci of the folate cycle genes with the development of the 2-3-degree fetal growth restriction syndrome &lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</article-title><trans-title-group xml:lang="en"><trans-title>&lt;strong&gt;The study of the association of polymorphic loci of the folate cycle genes with the development of the 2-3-degree fetal growth restriction syndrome &lt;/strong&gt;&lt;br /&gt;
&amp;nbsp;</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="ru"><surname>Efremova</surname><given-names>Olesya A.</given-names></name><name xml:lang="en"><surname>Efremova</surname><given-names>Olesya A.</given-names></name></name-alternatives><email>efremovaolesya@gmail.com</email></contrib></contrib-group><pub-date pub-type="epub"><year>2020</year></pub-date><volume>6</volume><issue>1</issue><fpage>0</fpage><lpage>0</lpage><self-uri content-type="pdf" xlink:href="/media/medicine/2020/1/document_март_2020-38-51.pdf" /><abstract xml:lang="ru"><p>Background: Folate cycle enzymes regulate key reactions in folate-mediated single-carbon metabolism. The folate cycle disturbances may be associated with the occurrence of placental insufficiency with fetal growth restriction syndrome (FGRS) in pregnant women, however, to date, the relationship of polymorphism of the folate cycle genes with the development of pregnancy pathology has not been examined in sufficient detail. The aim of the study: To study the association of polymorphic loci of the folate cycle genes with the development of 2-3-degree FGRS. Materials and methods: The sample for the study included 112 pregnant women with 2-3-degree FGRS and 243 pregnant women with normal birth weight. The polymorphic loci of the folate cycle gene rs1805087 of the MTR gene were studied, rs1801394 of the MTRR gene, rs1979277 of the SHMT1 gene, rs699517 of the TYMS gene, rs2790 of the TYMS gene involved in the formation of placental insufficiency and FGRS of the 2nd or 3rd degrees. The study was carried out by PCR using the appropriate oligonucleotide primers and probes, followed by analysis of polymorphisms by the detection method of TaqMan probes (real-time PCR). Association analysis was performed using gPLINK v2.050 software. Intergenic interactions in two- and three-locus models were analyzed using MDR method and its GMDR modifications. Results: It was shown that the T allele rs1979277 of the SHMT1 gene is associated with the development of 2-3-degree FGRS in the framework of additive (OR = 1.56, 95% Cl 1,10 - 2,22, p = 0,012, pperm = 0.011) and recessive (OR = 2.55, 95% Cl 1.24-5.22, p = 0,011, pperm = 0.007) models. The association of the G rs1805087 allele of the MTR gene with the formation of 2-3-degree FGRS was revealed in accordance with the recessive model (OR = 3.28, 95% Cl 1.14-9.47, p = 0.028, pperm = 0.014). Two 2-locus and one three-locus models of SNPxSNP interactions associated with the development of FGRS 2-3 degrees were identified. Significant models include three polymorphic loci &amp;ndash; rs1979277 SHMT1, rs1805087 MTR, and rs1801394 MTRR. Pairwise interaction rs1801394 MTRR x rs1979277 SHMT1 is the basis of the two most significant models of gene-gene interactions associated with the development of FGRS of 2-3 degrees. Conclusion: Polymorphic loci rs1979277 SHMT1, rs1805087 MTR and rs1801394 MTRR are associated with the development of FGRS of 2-3 degrees.</p></abstract><trans-abstract xml:lang="en"><p>Background: Folate cycle enzymes regulate key reactions in folate-mediated single-carbon metabolism. The folate cycle disturbances may be associated with the occurrence of placental insufficiency with fetal growth restriction syndrome (FGRS) in pregnant women, however, to date, the relationship of polymorphism of the folate cycle genes with the development of pregnancy pathology has not been examined in sufficient detail. The aim of the study: To study the association of polymorphic loci of the folate cycle genes with the development of 2-3-degree FGRS. Materials and methods: The sample for the study included 112 pregnant women with 2-3-degree FGRS and 243 pregnant women with normal birth weight. The polymorphic loci of the folate cycle gene rs1805087 of the MTR gene were studied, rs1801394 of the MTRR gene, rs1979277 of the SHMT1 gene, rs699517 of the TYMS gene, rs2790 of the TYMS gene involved in the formation of placental insufficiency and FGRS of the 2nd or 3rd degrees. The study was carried out by PCR using the appropriate oligonucleotide primers and probes, followed by analysis of polymorphisms by the detection method of TaqMan probes (real-time PCR). Association analysis was performed using gPLINK v2.050 software. Intergenic interactions in two- and three-locus models were analyzed using MDR method and its GMDR modifications. Results: It was shown that the T allele rs1979277 of the SHMT1 gene is associated with the development of 2-3-degree FGRS in the framework of additive (OR = 1.56, 95% Cl 1,10 - 2,22, p = 0,012, pperm = 0.011) and recessive (OR = 2.55, 95% Cl 1.24-5.22, p = 0,011, pperm = 0.007) models. The association of the G rs1805087 allele of the MTR gene with the formation of 2-3-degree FGRS was revealed in accordance with the recessive model (OR = 3.28, 95% Cl 1.14-9.47, p = 0.028, pperm = 0.014). Two 2-locus and one three-locus models of SNPxSNP interactions associated with the development of FGRS 2-3 degrees were identified. Significant models include three polymorphic loci &amp;ndash; rs1979277 SHMT1, rs1805087 MTR, and rs1801394 MTRR. Pairwise interaction rs1801394 MTRR x rs1979277 SHMT1 is the basis of the two most significant models of gene-gene interactions associated with the development of FGRS of 2-3 degrees. Conclusion: Polymorphic loci rs1979277 SHMT1, rs1805087 MTR and rs1801394 MTRR are associated with the development of FGRS of 2-3 degrees.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>polymorphism</kwd><kwd>associations</kwd><kwd>SNPхSNP interactions</kwd><kwd>placental insufficiency</kwd><kwd>fetal growth restriction syndrome</kwd><kwd>pregnancy</kwd><kwd>folate cycle</kwd></kwd-group><kwd-group xml:lang="en"><kwd>polymorphism</kwd><kwd>associations</kwd><kwd>SNPхSNP interactions</kwd><kwd>placental insufficiency</kwd><kwd>fetal growth restriction syndrome</kwd><kwd>pregnancy</kwd><kwd>folate cycle</kwd></kwd-group></article-meta></front><back><ref-list><title>Список литературы</title><ref id="B1"><mixed-citation>D&amp;rsquo;Souza SW, Solanky N, Guarino J, et al. Human Placental Arterial Distensibility, Birth Weight, and Body Size Are Positively Related to Fetal Homocysteine Concentration. Reprod Sci. 2017;24(7):1070-1078. DOI: 10.1177/1933719116678694</mixed-citation></ref><ref id="B2"><mixed-citation>Morales‐Rosell&amp;oacute; J, Dias T, Khalil A, et al. Birth-weight differences at term are explained by placental dysfunction and not by maternal ethnicity. Ultrasound Obstet Gynecol. 2018;52(4):488-493. DOI: 10.1002/uog.19025</mixed-citation></ref><ref id="B3"><mixed-citation>Zhang S, Regnault T, Barker P, et al. Placental adaptations in growth restriction. Nutrients. 2015;7:360-389. DOI: 10.3390/nu7010360</mixed-citation></ref><ref id="B4"><mixed-citation>Salavati N, Smies M, Ganzevoort W, et al. The Possible Role of Placental Morphometry in the Detection of Fetal Growth Restriction. Front. Physiol. 2019;9:1884. DOI: 10.3389/fphys.2018.01884</mixed-citation></ref><ref id="B5"><mixed-citation>Gordijn SJ, Beune IM, Ganzevoort W. Building consensus and standards in fetal growth restriction studies. Best Pract. Res. Clin. Obstet. Gynaecol. 2018;49:117-126. DOI: 10.1016/j.bpobgyn.2018.02.002</mixed-citation></ref><ref id="B6"><mixed-citation>Nardozza LMM, Caetano ACR, Zamarian ACP, et al. Fetal growth restriction: current knowledge. Arch. Gynecol. Obstet. 2017;295:1061-1077. DOI: 10.1007/s00404-017-4341-9</mixed-citation></ref><ref id="B7"><mixed-citation>Dasarathy J, Gruca LL, Bennett C, et al. Methionine metabolism in human pregnancy. Am J Clin Nutr. 2010;91(2):357-365. DOI: 10.3945/ajcn.2009.28457</mixed-citation></ref><ref id="B8"><mixed-citation>Ni AN, Fadeeva TJ, Vasilieva TG, et al. [Pathogenetic aspects of folic acid exchange disorder in case of delay of intrauterine fetal development]. Modern problems of science and education [Internet]. 2016 [cited 2019 Feb 20];2. Available from: http://www.science-education.ru/ru/article/view?id=24187.Russian.</mixed-citation></ref><ref id="B9"><mixed-citation>Ni AN, Fadeeva TJ, Vasilieva TG, et al. [Frequency of genetic markers of the folate cycle in newborns with delay of intrauterine development]. Russian Journal of Perinatology and Pediatrics. 2015;3:63-66. Russian.</mixed-citation></ref><ref id="B10"><mixed-citation>Larina TN, Suprun SV. [The Folate Cycle: Pathogenetic Mechanisms of Pregnancy Complications]. Bulletin of Physiology and Respiratory Pathology. 2018;70:113-120.</mixed-citation></ref><ref id="B11"><mixed-citation>Zhang Z, Yu L, Li S, et al. Association Study of Polymorphisms in Genes Relevant to Vitamin B12 and Folate Metabolism with Childhood Autism Spectrum Disorder in a Han Chinese Population. Med Sci Monit. 2018;24:370-376. DOI: 10.12659/MSM.905567</mixed-citation></ref><ref id="B12"><mixed-citation>Mamiy DD, Tatarkova EA, Tuguz AR, et al. [Polymorphisms of folate cycle genes associated with the threat of early termination of pregnancy in residents of the Republic of Adygea]. Journal of Adygei State University. Series 4: Natural-mathematical and technical sciences. 2018;1(212):103-111. Russian.</mixed-citation></ref><ref id="B13"><mixed-citation>Fekete K, Berti C, Cetin I, et al. Perinatal folate supply: relevance in health outcome parameters. Maternal and Child Nutrition. 2010;6(s2):23-38. DOI: https://doi.org/10.1111/j.1740-8709.2010.00261.x</mixed-citation></ref><ref id="B14"><mixed-citation>Bahari G, Hashemi M, Naderi M, et al. Association of SHMT1 gene polymorphisms with the risk of childhood acute lymphoblastic. Cell. Mol. Biol. 2016;62(2):45-51.</mixed-citation></ref><ref id="B15"><mixed-citation>Hui D, Lijie Y, Jie Y, et al. Correlations between the polymorphisms of serine hydroxymethyl-transferase 1 gene and the adverse reactions of high-dose methotrexate in children with acute lymphoblastic leukemia. Chinese Journal of Clinical Oncology. 2014;3:162-165. DOI: 10.3969/j.issn.1000-8179.20131420</mixed-citation></ref><ref id="B16"><mixed-citation>Mehrabani SZN, Shushizadeh MH, Abazari MF, et al. Association of SHMT1, MAZ, ERG, and L3MBTL3 gene polymorphisms with susceptibility to multiple sclerosis. Biochemical genetics. 2019;3(57):355-370. DOI: https://doi.org/10.1007/s10528-018-9894-1</mixed-citation></ref><ref id="B17"><mixed-citation>Rebekah PK, Tella S, Buragadda S, et al. Interaction between Maternal and Paternal SHMT1 C1420T Predisposes to Neural Tube Defects in the Fetus: Evidence from Case&amp;ndash;Control and Family‐Based Triad Approaches. Birth Defects Research. 2017;109(13):1020-1029. DOI:10.1002/bdr2.23623</mixed-citation></ref><ref id="B18"><mixed-citation>Copped&amp;egrave; F, Stoccoro A, Tannorella P, et al. Association of Polymorphisms in Genes Involved in One-Carbon Metabolism with MTHFR Methylation Levels. International Journal of Molecular Sciences. 2019;20(15):3754. DOI: https://doi.org/10.3390/ijms20153754</mixed-citation></ref><ref id="B19"><mixed-citation>Tian DD, Zhang CD, Wang LK. Relation between MTHFR and MTR gene polymorphisms and the efficacy of oral folic acid therapy for hyperhomocysteinemia. Chinese General Practice. 2016;19(12):1396-1407.</mixed-citation></ref><ref id="B20"><mixed-citation>Fetisova IN, Kolchkin AI, Fetisov NS. [Polymorphism of folate cycle genes in women with non-pregnancy]. Vestnik Ivanovskoy meditsinskoy akademii. 2019;24(1):33-36. Russian.</mixed-citation></ref><ref id="B21"><mixed-citation>Cho SH, Kim JH, An HJ, et al. Association of methionine synthase (rs1805087), methionine synthase reductase (rs1801394), and methylenetetrahydrofolate dehydrogenase 1 (rs2236225) genetic polymorphisms with recurrent implantation failure. Human Fertility. 2019 May 17:1-8. DOI: 10.1080/14647273.2019.1613679</mixed-citation></ref><ref id="B22"><mixed-citation>Niu Z, Hou X, Zhao H. Association of MTHFR, MTRR and MTR polymorphisms with breast cancer risk: a study in Chinese females. International Journal of Clinical and Experimental Pathology. 2017;10(6):7059-7066.</mixed-citation></ref><ref id="B23"><mixed-citation>Bakanova ML, Minina VI, Savchenko YA, et al. [Polymorphic variants of folate cycle genes in lung cancer patients]. Siberian Journal of Oncology. 2019;18(2):70-77. Russian.</mixed-citation></ref><ref id="B24"><mixed-citation>Wang C, Lu D, Ling Q, et al. Donor one‑carbon metabolism gene single nucleotide polymorphisms predict the susceptibility of cancer recurrence after liver transplantation. Gene. 2019;689:97-101. DOI: 10.1016/j.gene.2018.11.035</mixed-citation></ref><ref id="B25"><mixed-citation>Baghbani-Arani F, Telori MK, Asadi J, et al. Association of Two Single-Nucleotide Polymorphisms (rs1805087 and rs1801131) with Coronary Artery Disease in Golestan Population. Ann Mil Health Sci Res. 2017;15(1):e11473. DOI: 10.5812/amh.11473</mixed-citation></ref><ref id="B26"><mixed-citation>Churnosov MI, Necipelova EV, Tekunova TS, et al. [Population-genetic structure and analysis of the prevalence of candidate genes of a number of multi-factorial diseases among the population]. Scientific Bulletin of Belgorod State University. Series: Medicine. Pharmacy. 2008;6-2(46):34-39. Russian.</mixed-citation></ref><ref id="B27"><mixed-citation>Berezina OV, Pospelova TI. [Genes of folate metabolism in diffuse in-large-cell lymphoma]. Siberian Medical Journal (Irkutsk). 2018;153(2):9-13. Russian.</mixed-citation></ref></ref-list></back></article>