medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2024.11.47-54medgen-2573Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHIn silico исследование спектра ассоциированных с преэклампсией генетических вариантов в российской популяцииIn silico study of the spectrum of genetic variants associated with preeclampsia in the Russian populationЛазареваТ. Е.LazarevaT. E.

Лазарева Татьяна Евгеньевна

199034, г. Санкт-Петербург, Менделеевская линия, д.3

3, Mendeleevskaya Line, Saint Petersburg, 199034

tatiana.ev.lazareva@gmail.comБарбитовЮ. А.BarbitoffY. A.

199034, г. Санкт-Петербург, Менделеевская линия, д.3

3, Mendeleevskaya Line, Saint Petersburg, 199034

ВашуковаЕ. С.VashukovaE. S.

199034, г. Санкт-Петербург, Менделеевская линия, д.3

3, Mendeleevskaya Line, Saint Petersburg, 199034

НасыховаЮ. А.NasykhovaY. A.

199034, г. Санкт-Петербург, Менделеевская линия, д.3

3, Mendeleevskaya Line, Saint Petersburg, 199034

КоганИ. Ю.KoganI. Y.

199034, г. Санкт-Петербург, Менделеевская линия, д.3

3, Mendeleevskaya Line, Saint Petersburg, 199034

ГлотовА. С.GlotovA. S.

199034, г. Санкт-Петербург, Менделеевская линия, д.3

3, Mendeleevskaya Line, Saint Petersburg, 199034

БеспаловаО. Н.BespalovaO. N.

199034, г. Санкт-Петербург, Менделеевская линия, д.3

3, Mendeleevskaya Line, Saint Petersburg, 199034

ФГБНУ Научно- исследовательский институт акушерства,гинекологии и репродуктологии имени Д.О. ОттаРоссияResearch Institute of Obstetrics, Gynecology and Reproductology named after D.O. OttRussian Federation20240501202523114754Copyright © Лазарева Т.Е., Барбитов Ю.А., Вашукова Е.С., Насыхова Ю.А., Коган И.Ю., Глотов А.С., Беспалова О.Н., 20252025Лазарева Т.Е., Барбитов Ю.А., Вашукова Е.С., Насыхова Ю.А., Коган И.Ю., Глотов А.С., Беспалова О.Н.Lazareva T.E., Barbitoff Y.A., Vashukova E.S., Nasykhova Y.A., Kogan I.Y., Glotov A.S., Bespalova O.N.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/2573Введение

Введение. Преэклампсия (ПЭ) представляет собой одно из наиболее тяжелых гипертензивных осложнений беременности, встречающееся с частотой 2–15%. Это патологическое состояние характеризуется повышением артериального давления и несет значительный риск для здоровья матери и плода. Поиск ранних биомаркеров ПЭ остается приоритетной задачей для своевременной профилактики этого опасного состояния.

Цель

Цель: провести поиск in silico биомаркеров гипертензивных осложнений беременности, включая ПЭ, на основе результатов международных и отечественных полногеномных ассоциативных исследований (GWAS).

Материалы и методы

Материалы и методы. В настоящем исследовании проведена кросс-валидация суммарных статистик международных GWAS, посвященных гипертензивным осложнениям беременности, с результатами отечественного проекта Biobank Russia (BBRU).

Результаты

Результаты. Обнаружена ассоциация 44 однонуклеотидных вариантов (SNPs) с ПЭ и/или гипертензивными осложнениями беременности в целом как в поисковых, так и в валидационном GWAS. Для одного SNPs, варианта rs10843404 в гене PZP, ассоциация достигла статистической значимости (p < 0,05) в отечественном GWAS, для 4 других SNPs в генах FLT1, FGF5 наблюдалась тенденция к статистической значимости (p<0,1).

Выводы

Выводы. Результаты репликативного анализа в сочетании с данными литературы свидетельствуют о значимой роли продукта гена PZP в развитии гипертензивных осложнений беременности. Небольшое число реплицированных локусов в отечественной когорте может указывать как на различия в генетической природе ПЭ между популяциями, так и на необходимость проведения исследования на более крупных выборках, что позволит повысить статистическую мощность и сформировать более полное представление о генетических факторах риска ПЭ в российской популяции.

Background

Background. Preeclampsia (PE) is a serious complication related to high blood pressure during pregnancy, affecting approximately 2-15% of pregnant women. This condition is marked by elevated blood pressure and poses substantial risks to both maternal and fetal health. Identifying early biomarkers for PE is a key focus in the effort to prevent this potentially dangerous condition in a timely manner.

Aim

Aim: The aim of this study was to identify potential in silico biomarkers for hypertensive complications during pregnancy by analyzing findings from both international and domestic genome-wide association studies (GWAS).

Methods

Methods. The research involved the examination of summary statistics from international GWAS focused on hypertensive complications of pregnancy, which were then cross-validated against data from the Biobank Russia (BBRU) project.

Results

Results. The analysis revealed 44 single nucleotide polymorphisms (SNPs) linked to preeclampsia (PE) and/or other hypertensive complications during pregnancy across both discovery and validating GWAS. Notably, the rs10843404 SNP variant in the PZP gene was statistically significant (p < 0.05) in the domestic GWAS. Additionally, four other SNPs located in the FLT1 and FGF5 genes showed a tendency toward statistical significance (p < 0.1).

Conclusions

Conclusions. The findings from the replication analysis, along with literature data, indicate that the product of the PZP plays a crucial role in the development of hypertensive forms of PE. The limited number of replicated loci in the Russian cohort may reflect genetic differences in PE across populations, highlighting the need for further studies involving larger sample sizes to enhance statistical power and provide a more comprehensive understanding of genetic risk factors for PE in the Russian population.

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