akusherstvoObstetrics, Gynecology and ReproductionАкушерство, Гинекология и Репродукция2313-73472500-3194IRBIS LLC10.17749/2313-7347/ob.gyn.rep.2024.466akusherstvo-1878Research ArticleОRIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИMTRR gene rs1801394 polymorphism is associated with neonatal birth weight in pregnant women with fetal growth retardationПолиморфизм rs1801394 гена MTRR ассоциирован с массой тела новорожденного у беременных с задержкой роста плодаhttps://orcid.org/0009-0004-6123-4086РешетниковаЮ. Н.ReshetnikovaYu. N.

Решетникова Юлия Николаевна – аспирант кафедры медико-биологических дисциплин

308015 Белгород, ул. Победы, д. 85

Yulia N. Reshetnikova – MD, Postgraduate Student, Department of Medical and Biological Disciplines, Medical Institute

85 Pobedy Str., Belgorod 308015

https://orcid.org/0000-0002-5652-0166ПономаренкоИ. В.PonomarenkoI. V.

Пономаренко Ирина Васильевна – д.м.н., доцент, профессор кафедры медико-биологических дисциплин. Scopus Author ID: 57190225823

308015 Белгород, ул. Победы, д. 85

Irina V. Ponomarenko – MD, Dr Med Sci, Associate Professor, Professor, Department of Medical and Biological Disciplines, Medical Institute

Scopus Author ID: 57190225823

85 Pobedy Str., Belgorod 308015

https://orcid.org/0009-0009-0312-0829ЧурносовВ. М.ChurnosovV. М.

Чурносов Владимир Михайлович – аспирант кафедры медико-биологических дисциплин

308015 Белгород, ул. Победы, д. 85

Vladimir М. Churnosov – MD, Postgraduate Student, Department of Medical and Biological Disciplines, Medical Institute

85 Pobedy Str., Belgorod 308015

https://orcid.org/0009-0007-8519-4594ПономаренкоМ. С.PonomarenkoM. S.

Пономаренко Марина Сергеевна – аспирант кафедры медико-биологических дисциплин

308015 Белгород, ул. Победы, д. 85

Marina S. Ponomarenko – MD, Postgraduate Student, Department of Medical and Biological Disciplines, Medical Institute

85 Pobedy Str., Belgorod 308015

https://orcid.org/0000-0003-1254-6134ЧурносовМ. И.ChurnosovM. I.

Чурносов Михаил Иванович – д.м.н., профессор, зав. кафедрой медико-биологических дисциплин. Scopus Author ID: 6601948788

308015 Белгород, ул. Победы, д. 85

Mikhail I. Churnosov – MD, Dr Med Sci, Professor, Head of the Department of Medical and Biological Disciplines, Medical Institute. Scopus Author ID: 6601948788

85 Pobedy Str., Belgorod 308015

https://orcid.org/0000-0002-5429-6666РешетниковЕ. А.ReshetnikovE. A.

Решетников Евгений Александрович – д.б.н., доцент, профессор кафедры медико-биологических дисциплин. Scopus Author ID: 7006183889

308015 Белгород, ул. Победы, д. 85

Evgeniy А. Reshetnikov – MD, Dr Biol Sci, Associate Professor, Professor, Department of Medical and Biological Disciplines, Medical Institute. Scopus Author ID: 7006183889

85 Pobedy Str., Belgorod 308015

reshetnikov@bsu.edu.ruФГАОУ ВО «Белгородский государственный национальный исследовательский университет»РоссияBelgorod National Research UniversityRussian Federation2024150120241814654Copyright © Reshetnikova Y.N., Ponomarenko I.V., Churnosov V.М., Ponomarenko M.S., Churnosov M.I., Reshetnikov E.A., 20242024Решетникова Ю.Н., Пономаренко И.В., Чурносов В.М., Пономаренко М.С., Чурносов М.И., Решетников Е.А.Reshetnikova Y.N., Ponomarenko I.V., Churnosov V.М., Ponomarenko M.S., Churnosov M.I., Reshetnikov E.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.gynecology.su/jour/article/view/1878Aim

Aim: to assess associations between folate cycle gene polymorphism and neonatal birth weight in pregnant women with fetal growth retardation (FGR) and related functional effects in population of the Central Black Earth Region.

Materials and Methods

Materials and Methods. 98 cases of women with FGR were enrolled to a retrospective molecular and genetic screening to assess prevalence 5 SNPs (single nucleotide polymorphisms) in genes involved in folic acid cycle and methionine metabolism (rs699517 TYMS, rs2790 TYMS, rs1979277 SHMT1, rs1805087 MTR, rs1801394 MTRR).

Results

Results. It was found out that allele A of the rs1801394 MTRR was associated with a lower neonatal birth weight (recessive model: β = –0.34 ± 0.13; p = 0.009). This polymorphic locus exerts crucial functional effects by determining the amino acid substitution in methionine synthase reductase (Ile22Met) localized in the region of modified histones, which mark enhancers and promoters in ectoderm, endoderm and mesoderm cell cultures, primary osteoblast cells, brain, fat nuclei, skeletal muscles, etc. In addition, rs1801394 MTRR is found DNA sites (motifs) responsible for sensitivity to transcription factors STAT and TBX5 being also related to MTRR gene mRNA expression level in subcutaneous and visceral adipose tissue, thyroid gland, fibroblast cell culture as well as various brain regions.

Conclusion

Conclusion. Thus, the allele A of the rs1801394 polymorphism in MTRR gene is a risk factor for a lower neonatal birth weight.

Цель

Цель: изучение взаимосвязи полиморфизма генов метаболизма фолиевой кислоты и метионина с массой тела новорожденных у беременных с задержкой роста плода (ЗРП) в популяции Центрально-Черноземного региона России.

Материалы и методы

Материалы и методы. В ретроспективном молекулярно-генетическом исследовании у 98 беременных с ЗРП (n = 98) изучено 5 однонуклеотидных полиморфных локусов (англ. single nucleotide polymorphism, SNP) генов, участвующих в процессах обмена фолиевой кислоты и метионина (rs699517 TYMS, rs2790 TYMS, rs1979277 SHMT1, rs1805087 MTR, rs1801394 MTRR).

Результаты

Результаты. Установлены ассоциации аллеля А rs1801394 MTRR с более низкой массой тела новорожденного у женщин с ЗРП в рамках рецессивной модели (β = –0,34 ± 0,13; p = 0,009). Данный полиморфный локус обладает важными функциональными эффектами. Он определяет аминокислотную замену в метионин-синтаза-редуктазе (Ile22Met), локализован в регионе модифицированных гистонов, маркирующих энхансеры и промоторы в культуре клеток эктодермы, энтодермы и мезодермы, первичных клетках остеобластов, головном мозге, жировых ядрах, скелетных мышцах и др.; определяет чувствительность ДНК к двум факторам транскрипции (STAT и TBX5); связан с уровнем экспрессии мРНК гена MTRR в подкожной и висцеральной жировой ткани, щитовидной железе, культуре клеток фибробластов, различных отделах головного мозга.

Заключение

Заключение. Таким образом, аллель А полиморфизма rs1801394 гена MTRR является фактором риска более низкой массы тела новорожденного.

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