ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМП10.25789/YMJ.2019.68.03ymj-1135Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHРепликативный анализ факторов наследственной тромбофилии в развитии преэклампсии в якутской популяцииReplicative analysis of hereditary thrombophilia factors in the development of preeclampsia in the Yakut populationСереброваВ. Н.SerebrovaV. N.

Сереброва Виктория Николаевна – к.м.н., м.н.с. НИИ медицинской генетики

Serebrova Victoria Nicolaevna – Candidate of Medical Sciences, Junior researcher

Nab. Ushaiki, 10, Tomsk, 634050

vika.serebrova@medgenetics.ruТрифоноваЕ. А.TrifonovaE. A.

Трифонова Екатерина Александровна – к.м.н., н.с. НИИ медицинской генетики

Trifonova Ekaterina Aleksandrovna – Candidate of Medical Sciences, Researcher

Nab. Ushaiki, 10, Tomsk, 634050

ekaterina-trifonova@medgenetics.ruПавловаК. К.PavlovaK. K.

Павлова Кюнна Константиновна – к.м.н., врач лабораторный генетик

г. Якутск

Pavlova Kunna Konstantinovna – Candidate of Medical Sciences, doctor - laboratory geneticist

Sergelyakhskoye hwy, 4, Yakutsk, 677010

rb1ncm@mail.ruВорожищеваА. Ю.VorozhishchevaA. Yu.

Ворожищева Анна Юрьевна – к.м.н., зав. клинич. лаб.

Vorozhishcheva Anna Yuryevna – Candidate of Medical Sciences, Head of Clinical Laboratory

Bardina Ave., 28, Novokuznetsk, 654057

laptevaanna2@rambler.ruКуртановХ. А.KurtanovKh. A.

Куртанов Харитон Алексеевич – к.м.н., гл.н.с. – руковод. Отдела

Kurtanov Khariton Alekseevich, Candidate of Medical Sciences, Chief Researcher, Head of Molecular Genetics Department

Sergelyakhskoye hwy, 4, Yakutsk, 677000

hariton_kurtanov@mail.ruПавловаН. И.PavlovaN. I.

Павлова Надежда Ивановна – к.б.н., в.н.с. – руковод. лаб.

Pavlova Nadezhda Ivanovna - Candidate of biological Sciences, temporary acting chief scientific officer - head of the laboratory of heritable pathology

Sergelyakhskoye hwy, 4, Yakutsk, 677000

solnishko_84@inbox.ruСтепановВ. А.StepanovV. A.

Степанов Вадим Анатольевич – членкорр. РАН, д.б.н., проф., врио директора, руковод. лаб. НИИ медицинской генетики

Stepanov Vadim Anatolevich – Corresponding Member of the Russian Academy of Sciences, Doctor of Biology Sciences, Professor. Acting Director;

Head of the Laboratory of Evolutionary genetics

Nab. Ushaiki, 10, Tomsk, 634050

vadim.stepanov@medgenetics.ruТомский НИМЦРоссияResearch Institute of Medical Genetics, Tomsk NRMCRussian FederationРБ №1 – НЦМРоссияState Autonomous Institution of the Republic of Sakha (Yakutia) “Republican Hospital No. 1-National Center of Medicine”Russian FederationНовокузнецкая городская клиническая больница №1РоссияThe government owned autonomous health-care institution of Kemerovo Oblast «Novokuznetsk municipal clinical hospital № 1»Russian FederationЯНЦ КМПРоссияYakut Science Centre of complex medical problemsRussian FederationТомский НИМЦРоссияTomsk National Research Medical Center of the Russian Academy of Sciences (Tomsk NRMC); Institute of Medical Genetics, Tomsk NRMCRussian Federation201929082025041519Copyright © Сереброва В.Н., Трифонова Е.А., Павлова К.К., Ворожищева А.Ю., Куртанов Х.А., Павлова Н.И., Степанов В.А., 20252025Сереброва В.Н., Трифонова Е.А., Павлова К.К., Ворожищева А.Ю., Куртанов Х.А., Павлова Н.И., Степанов В.А.Serebrova V.N., Trifonova E.A., Pavlova K.K., Vorozhishcheva A.Y., Kurtanov K.A., Pavlova N.I., Stepanov V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ymj.elpub.ru/jour/article/view/1135

Проведен репликативный анализ ассоциаций однонуклеотидных полиморфных вариантов четырех наиболее значимых генов наследственной тромбофилии с развитием преклампсии (ПЭ) в популяции якутов: rs1801133 (C677T) гена MTHFR, rs1799963 (G20210A) гена F2, rs6025 (G1691A) гена F5 и rs1799889 (-675 4G/5G) гена SERPINE1. Результаты исследования свидетельствуют о статистически значимой ассоциации аллеля 4G полиморфного варианта rs1799889 (-675 4G/5G) гена SERPINE1 с формированием наследственной предрасположенности к развитию данного заболевания у якутов как в общей группе больных, так и подгруппе пациенток с тяжелой степенью ПЭ.

We conducted a replicative associations analysis of the single-nucleotide polymorphisms of 4 most significant genes of hereditary thrombophilia with the development of preeclampsia (PE) in the Yakut population: rs1801133 (C677T) in the MTHFR gene, rs1799963 (G20210A) in the F2, rs6025 (G999A) in the F5 gene and rs1799889 (-675 4G/5G) in the SERPINE1 gene. The results of this study indicate a statistically significant association of 4G allele of polymorphic variant rs1799889 (-675 4G/5G) in the SERPINE1 gene in formation of a hereditary predisposition to the development of this pregnancy complication in Yakuts, both in the general group of patients and in the subgroup of patients with severe PE.

преэклампсиянаследственная тромбофилияассоциативное исследованиеpreeclampsiahereditary thrombophiliaassociation studyРабота выполнена при финансовой поддержке РФФИ (грант №18-44-700007).This work was supported by the Russian Foundation for Basic Research (Grant No. 18-44-700007).ReferencesАнализ роли наследственной тромбофилии в развитии осложненного течения беременности / Е.А. Трифонова [и др.] // Фундаментальные исследования. – 2012. – №10. – С. 337-344.Analysis of the role of hereditary thrombophilia in developing severe gestation course / E.A. Trifonova [et al.] // Fundamental research. – 2013. – Vol. 10. – P.337-344.Ангиогенные ростовые факторы и патогенез преэклампсии / Н.В. Башмакова [и др.] // Российский вестник акушера-гинеколога. – 2017. – № 17(5). – С. 7–12.Angiogenic growth factors and the pathogenesis of preeclampsia / N.V. Bashmakova [et al.] // Russian Bulletin of Obstetrician-Gynecologist. – 2017. – Vol. 17(5). – P. 7–12.Атабаева Х.Л. Основные принципы подготовки к беременности и ее ведение у беременных с преэклампсией на фоне выявленной тромбофилии / Х.Л. Атабаева // Акушерство, гинекология и репродукция. – 2016. – № 10(4). – С. 30-38.Atabaeva H.L. Principles of pregravid preparation and management of pregnant women with preeclampsia in the background of thrombophilia / H.L. Atabaeva // Obstetrics, gynecology and reproduction. – 2016. – Vol. 10(4). – P. 30-38.Баранов В.С. Генетический паспорт – основа индивидуальной и предиктивной медицины / В.С. Баранов. – СПб., 2009. – 528 с.Baranov V.S. Genetic passport - the basis of individual and predictive medicine / V.S. Baranov. – SPb, 2009. – P. 528.Макаров О.В. Клинические аспекты преэклампсии / О.В. Макаров, Е.В. Волкова, Л.С. Джохадзе // Российский вестник акушера-гинеколога. – 2011. – № 11(4). – С. 29-35.Makarov O.V. Clinical aspects of preeclampsia / O.V. Makarov, E.V. Volkova, L.S. Dzhokhadze // Russian Bulletin of the obstetrician-gynecologist. – 2011. – Vol. 11(4). – P. 29-35.Методическое письмо Министерства здравоохранения Российской Федерации «Аудит критических акушерских состояний в Российской Федерации в 2016» / О.С. Филиппов [и др.]. – М., 2017. – 44 с.Methodical letter of the Ministry of Health of the Russian Federation «Audit of critical obstetric conditions in the Russian Federation in 2016» O.S. Filippov [et al.]. – M., 2013. – P. 73.Патогенетические механизмы развития преэклампсии у женщин с метаболическим синдромом / Е.Б. Передеряева [и др.] // Акушерство, гинекология и репродукция. – 2015. – № 9(3). – С.54-65.The pathogenetic mechanisms of development of preeclampsia in women with metabolic syndrome / E.B. Perederyaeva [et al.] // Obstetrics, gynecology and reproduction. – 2015. – Vol. 9(3). – P.54-65. (In Russ.)].Роль полиморфизмов генов еNOS, ACE и MTHFR в развитии гестоза в якутской популяции / К.К. Павлова [и др.] // Якутский медицинский журнал. – 2010. – № 3(31). – С. 28-31.The role of еNOS, ACE and MTHFR genes polymorphisms in the development of gestosis in the Yakut population / K.K. Pavlova [et al.] // Yakut Medical Journal. – 2010. – Vol. 3(31). – P. 28-31.Роль факторов наследственной предрасположенности в развитии преэклампсии: обзор данных метаанализов / Е.А. Трифонова [и др.] // Молекулярная медицина. – 2016. – Т. 14, № 1. – С. 8-14.Factors of hereditary predisposition for preeclampsia: generalization of data of meta-analyses / E.A. Trifonova [et al.] // Molecular medicine. – 2016. – Vol. 14(1). – P. 8-14.Таюрская А.С. Частота преэклампсии и ранние специфические метаболические маркеры дизадаптации организма беременных при преэклампсии в условиях Крайнего Севера / А.С. Таюрская // Бюллетень ВСНЦ СО РАМН. – 2013. – N. 94. – C. 71-73.Tayurskaya A.S. Preeclampsia frequency and early specific metabolic markers of dysadaptation in preeclampsia in pregnant women at Far North / A.S. Tayurskaya // VSNTS SO RAMN Bulleten. – 2013. – Vol. 94. – P. 71-73.Федеральные клинические рекомендации. Гипертензивные расстройства во время беременности, в родах и послеродовом периоде. Преэклампсия. Эклампсия. Российское общество акушеров-гинекологов / Л.В. Адамян [и др.]. – М., 2013. – 73 с.Federal clinical guidelines. Hypertensive disorders in pregnancy, in childbirth, and the postpartum period. Preeclampsia. Eclampsia. Russian Society of Obstetricians and Gynecologists / L.V. Adamyan [et al.]. – M., 2013. – P. 73.Association Between Gene Polymorphisms on Chromosome 1 and Susceptibility to Pre-Eclampsia: An Updated Meta-Analysis / G. Zhang [et al.] // Med Sci Monit. – 2016. – Vol. 22. – P. 2202-2214.Association Between Gene Polymorphisms on Chromosome 1 and Susceptibility to Pre-Eclampsia: An Updated Meta-Analysis / G. Zhang [et al.] // Med Sci Monit. – 2016. – Vol. 22. – P. 2202-2214.Association between plasminogen activator inhibitor 1 gene polymorphisms and preeclampsia / D. Fabbro [et al.] // Gynecol Obstet Invest. – 2003. – Vol. 56(1). – P. 17-22.Association between plasminogen activator inhibitor 1 gene polymorphisms and preeclampsia / D. Fabbro [et al.] // Gynecol Obstet Invest. – 2003. – Vol. 56(1). – P. 17-22.Association between the SERPINE1 (PAI-1) 4G/5G insertion/deletion promoter polymorphism (rs1799889) and preeclampsia: a systematic review and metaanalysis / L. Zhao [et al.] // Mol Hum Reprod. – 2013. – Vol. 19(3). – P. 136-143.Association between the SERPINE1 (PAI-1) 4G/5G insertion/deletion promoter polymorphism (rs1799889) and preeclampsia: a systematic review and metaanalysis / L. Zhao [et al.] // Mol Hum Reprod. – 2013. – Vol. 19(3). – P. 136-143.Association between thrombophilia gene polymorphisms and preeclampsia: a meta-analysis / X. Wang [et al.] // PLoS. One. – 2014. – Vol. 9(6). – e100789. DOI: 10.1371/journal.pone.0100789.Association between thrombophilia gene polymorphisms and preeclampsia: a meta-analysis / X. Wang [et al.] // PLoS. One. – 2014. – Vol. 9(6). – e100789. DOI: 10.1371/journal.pone.0100789.Association of gene polymorphisms of FV, FII, MTHFR, SERPINE1, CTLA4, IL10, and TNFalpha with pre-eclampsia in Chinese women / L. Zhou [et al.] // Inflamm Res. – 2016. – Vol. 65(9). – P. 717-724. DOI: 10.1007/s00011-016-0953-y.Association of gene polymorphisms of FV, FII, MTHFR, SERPINE1, CTLA4, IL10, and TNFalpha with pre-eclampsia in Chinese women / L. Zhou [et al.] // Inflamm Res. – 2016. – Vol. 65(9). – P. 717-724. DOI: 10.1007/s00011-016-0953-y.Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for preeclampsia: a meta-analysis / X. Wu [et al.] // J Assist Reprod Genet. – 2015. – Vol. 32(5). – P. 797-805. DOI: 10.1007/s10815-014-0408-8.Folate metabolism gene polymorphisms MTHFR C677T and A1298C and risk for preeclampsia: a meta-analysis / X. Wu [et al.] // J Assist Reprod Genet. – 2015. – Vol. 32(5). – P. 797-805. DOI: 10.1007/s10815-014-0408-8.Genetic thrombophilia and markers of endothelial activation in patients with preeclampsia / J.C. Rojas [et al.] // Ginecol Obstet Mex. – 2010. – Vol. 78(8). – P. 401-409.Genetic thrombophilia and markers of endothelial activation in patients with preeclampsia / J.C. Rojas [et al.] // Ginecol Obstet Mex. – 2010. – Vol. 78(8). – P. 401-409.Global and regional estimates of preeclampsia and eclampsia: a systematic review / E. Abalos [et al.] // Eur J Obstet Gynecol Reprod Biol. – 2013. – Vol. 170(1). – P. 1-7. DOI:10.1016/j.ejogrb.2013.05.005 pmid:23746796.Global and regional estimates of preeclampsia and eclampsia: a systematic review / E. Abalos [et al.] // Eur J Obstet Gynecol Reprod Biol. – 2013. – Vol. 170(1). – P. 1-7. DOI:10.1016/j.ejogrb.2013.05.005 pmid:23746796.Kamal, M. Do serum angiopoietin-1, angiopoietin-2, and their receptor Tie-2 and 4G/5G variant of PAI-1 gene have a role in the pathogenesis of preeclampsia? / M. Kamal, W. El-Khayat // J Investig Med. – 2011. – Vol. 59(7). – P. 1147-1150. DOI: 10.2310/JIM.0b013e31822c5bdf.Kamal, M. Do serum angiopoietin-1, angiopoietin-2, and their receptor Tie-2 and 4G/5G variant of PAI-1 gene have a role in the pathogenesis of preeclampsia? / M. Kamal, W. El-Khayat // J Investig Med. – 2011. – Vol. 59(7). – P. 1147-1150. DOI: 10.2310/JIM.0b013e31822c5bdf.Maternal Ethnicity and Preeclampsia in New York City, 1995-2003 / J. Gong [et al.] // Paediatr Perinat Epidemiol. – 2012. – Vol. 26(1). – P. 45-52. DOI: 10.1111/j.1365-3016.2011.01222.x.Maternal Ethnicity and Preeclampsia in New York City, 1995-2003 / J. Gong [et al.] // Paediatr Perinat Epidemiol. – 2012. – Vol. 26(1). – P. 45-52. DOI: 10.1111/j.1365-3016.2011.01222.x.Morgan, J.A. Association of plasminogen activator inhibitor-type 1 (-675 4G/5G) polymorphism with pre-eclampsia: systematic review / J.A. Morgan, S. Bombell, W. McGuire // PLoS One. – 2013. – Vol. 8(2). e56907. DOI: 10.1371/journal.pone.0056907.Morgan, J.A. Association of plasminogen activator inhibitor-type 1 (-675 4G/5G) polymorphism with pre-eclampsia: systematic review / J.A. Morgan, S. Bombell, W. McGuire // PLoS One. – 2013. – Vol. 8(2). e56907. DOI: 10.1371/journal.pone.0056907.Patterns of pregnancy-related hypertension in black and white women / A.S. Bryant [et al.] // Hypertens Pregnancy. – 2005. – Vol. 24(3). – P. 281-290.Patterns of pregnancy-related hypertension in black and white women / A.S. Bryant [et al.] // Hypertens Pregnancy. – 2005. – Vol. 24(3). – P. 281-290.Polymorphisms of the methylenetetrahydrofolate reductase gene (C677T and A1298C) in the placenta of pregnancies complicated with preeclampsia / P. Chedraui, [et al.] // Gynecol Endocrinol. – 2015. – Vol. 31(7). – P. 569-572. DOI: 10.3109/09513590.2015.1031104.Polymorphisms of the methylenetetrahydrofolate reductase gene (C677T and A1298C) in the placenta of pregnancies complicated with preeclampsia / P. Chedraui, [et al.] // Gynecol Endocrinol. – 2015. – Vol. 31(7). – P. 569-572. DOI: 10.3109/09513590.2015.1031104.Preeclampsia and its interaction with common variants in thrombophilia genes / M.P. De Maat [et al.] // J Thromb Haemost. – 2004. – Vol. 2(9). – P. 1588-1593.Preeclampsia and its interaction with common variants in thrombophilia genes / M.P. De Maat [et al.] // J Thromb Haemost. – 2004. – Vol. 2(9). – P. 1588-1593.Preeclampsia in North Indian women: the contribution of genetic polymorphisms / S. Aggarwal [et al.] // J Obstet Gynaecol Res. – 2011. – Vol. 37(10). – P. 1335-1341. DOI: 10.1111/j.1447-0756.2010.01523.x.Preeclampsia in North Indian women: the contribution of genetic polymorphisms / S. Aggarwal [et al.] // J Obstet Gynaecol Res. – 2011. – Vol. 37(10). – P. 1335-1341. DOI: 10.1111/j.1447-0756.2010.01523.x.Pre-eclampsia: pathophysiology and clinical implications / G.J. Burton [et al.] // BMJ. – 2019. – Vol. 366(l2381). – P. 1-15. DOI:10.1136/bmj.l2381.Pre-eclampsia: pathophysiology and clinical implications / G.J. Burton [et al.] // BMJ. – 2019. – Vol. 366(l2381). – P. 1-15. DOI:10.1136/bmj.l2381.Pregnancy, parturition and preeclampsia in women of African ancestry / A. Nakimuli [et al.] // Am J Obstet Gynecol. – 2014. – Vol. 210(6). – P. 510-520.e1. DOI:10.1016/j.ajog.2013.10.879 pmid:24184340.Pregnancy, parturition and preeclampsia in women of African ancestry / A. Nakimuli [et al.] // Am J Obstet Gynecol. – 2014. – Vol. 210(6). – P. 510-520.e1. DOI:10.1016/j.ajog.2013.10.879 pmid:24184340.Racial disparity in hypertensive disorders of pregnancy in New York State: a 10-year longitudinal population-based study / M. Tanaka [et al.] // Am J Public Health. – 2007. – Vol. 97(1). – P. 163-170.Racial disparity in hypertensive disorders of pregnancy in New York State: a 10-year longitudinal population-based study / M. Tanaka [et al.] // Am J Public Health. – 2007. – Vol. 97(1). – P. 163-170.The G20210A prothrombin-gene mutation and the plasminogen activator inhibitor (PAI-1) 5G/5G genotype are associated with early onset of severe preeclampsia / A. Gerhardt [et al.] // J Thromb Haemost. – 2005. – Vol. 3(4). – P. 686-691.The G20210A prothrombin-gene mutation and the plasminogen activator inhibitor (PAI-1) 5G/5G genotype are associated with early onset of severe preeclampsia / A. Gerhardt [et al.] // J Thromb Haemost. – 2005. – Vol. 3(4). – P. 686-691.The significance of genetic polymorphisms of factor V Leiden and prothrombin in the preeclamptic Polish women / A. Seremak-Mrozikiewicz [et al.] // J Thromb Thrombolysis. – 2010. – Vol. 30(1). – P. 97-104. DOI: 10.1007/s11239-009-0432-1.The significance of genetic polymorphisms of factor V Leiden and prothrombin in the preeclamptic Polish women / A. Seremak-Mrozikiewicz [et al.] // J Thromb Thrombolysis. – 2010. – Vol. 30(1). – P. 97-104. DOI: 10.1007/s11239-009-0432-1.

The authors declare that there are no conflicts of interest present.