medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2018.03.34-42medgen-405Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHРоль генов ангиогенеза и эндотелиальной дисфункции в формировании структуры наследственной предрасположенности к привычному невынашиванию беременностиThe role of angiogenesis and endothelial dysfunction genes to recurrent miscarriage susceptibilityТрифоноваЕ. А.TrifonovaE. A.ekaterina.trifonova@medgenetics.ruГаньжаО. А.GanzhaO. A.noemail@neicon.ruГабидулинаТ. В.GabidulinaT. V.noemail@neicon.ruСтепановВ. А.StepanovV. A.noemail@neicon.ruНИИ медицинской генетики, Томский национальный исследовательский медицинский центр РАН; ФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава РоссииРоссияResearch Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences; Siberian State Medical UniversityRussian FederationФГБОУ ВО «Сибирский государственный медицинский университет» Минздрава РоссииРоссияSiberian State Medical UniversityRussian FederationНИИ медицинской генетики, Томский национальный исследовательский медицинский центр РАНРоссияResearch Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of SciencesRussian Federation2018030420181733442Copyright © Трифонова Е.А., Ганьжа О.А., Габидулина Т.В., Степанов В.А., 20182018Трифонова Е.А., Ганьжа О.А., Габидулина Т.В., Степанов В.А.Trifonova E.A., Ganzha O.A., Gabidulina T.V., 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://www.medgen-journal.ru/jour/article/view/405

В настоящее время продолжается активный поиск генетических предикторов привычного невынашивания беременности (ПНБ), являющегося одной из наиболее важных проблем, оказывающих отрицательное воздействие на репродуктивное здоровье женщины и обусловливающих высокие показатели перинатальной заболеваемости и смертности. Поскольку невынашивание беременности рассматривается большинством авторов как многофакторное состояние, то ген-генные взаимодействия могут играть важную роль в этиологии данного заболевания, являясь одним из источников его «недостающей наследуемости» («missing heritability»). В связи с этим, целью представленной работы являлся анализ ассоциации с ПНБ полиморфных вариантов генов ангиогенеза и эндотелиальной дисфункции, а также поиск межгенных взаимодействий, играющих значимую роль в формировании генетической предрасположенности к данной патологии. Показано, что в качестве генетических факторов, ассоциированных с предрасположенностью к данной патологии в русской этнической группе можно выделить аллели 677T гена MTHFR и 894T гена NOS3 , а также генотипы 936CT и 936TT гена VEGF . Продемонстрирована значимая роль аддитивного и эпистатического эффектов межгенных взаимодействий изученных полиморфных вариантов генов SERPINE-1 , ACE , NOS3 , MTHFR и VEGF в формировании генетической архитектуры ПНБ. Полученные результаты свидетельствуют о более высокой информативности оценки риска развития невынашивания беременности при анализе комбинации генотипов нескольких аллельных вариантов по сравнению с данными, полученными на уровне отдельных полиморфных маркеров.

The roles of genetic polymorphisms in the pathogenesis of recurrent miscarriage (RM) have been intensively studied. The main problems of active search for genetic predictors RM has become the phenomenon of «missing heritability». Complex diseases, including miscarriage are believed to have a polygenic basis and gene-gene interactions can play a significant role in the etiology of the disease. Gene-gene interactions can be a source of RM «missing heritability». This study was conducted to investigate the association of gene-gene interaction of angiogenesis and endothelial dysfunction genes polymorphisms and RM. It is shown that alleles of the 677T gene of the MTHFR gene, 894T of the NOS3 gene, genotypes of the 936CT and 936TT of the VEGF gene are associated with a predisposition to this pathology in the Russian ethnic group. The significant role of additive and epistatic effects in the intergenic interactions of the polymorphic variants of the SERPINE-1, ACE, NOS3, MTHFR , and VEGF genes to recurrent miscarriage susceptibility has been demonstrated. It has been shown that the analysis of a combination of genotypes of several allelic variants is more informative in assessing the risk of developing miscarriage than an association analysis at the level of single polymorphic markers.

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