medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2024.04.45-53medgen-2462Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHВлияние генетических вариантов GSTP1 и GPX4 и их межгенного взаимодействия на тяжесть течения COVID-19Effects of GSTP1 and GPX4 genetic variants and their gene-gene interaction on the severity of COVID-19ИдМ. А.EidM. A.

344006, г. Ростов-на-Дону, ул. Большая Садовая, д. 105/42

105/42, Bolshaya Sadovaya st., Rostov-on-Don, 344006

moez1995.mae@gmail.comАлександроваА. А.AleksandrovaA. A.

344006, г. Ростов-на-Дону, ул. Большая Садовая, д. 105/42;

344034, г. Ростов-на-Дону, ул. Загорская, д. 23, к. А, офис 1

105/42, Bolshaya Sadovaya st., Rostov-on-Don, 344006;

23A, Zagorskaya st., Rostov-on-Don, 344034

ЗатонскийС. А.ZatonskyS. A.

344034, г. Ростов-на-Дону, ул. Загорская, д. 23, к. А, офис 1;

344022, г. Ростов-на-Дону, ул. Суворова, д. 119

23A, Zagorskaya st., Rostov-on-Don, 344034;

119, Suvorova st., Rostov-on-Don, 344022

ГутниковаЛ. В.GutnikovaL. V.

344006, г. Ростов-на-Дону, ул. Большая Садовая, д. 105/42

105/42, Bolshaya Sadovaya st., Rostov-on-Don, 344006

ШкуратТ. П.ShkuratT. P.

344006, г. Ростов-на-Дону, ул. Большая Садовая, д. 105/42;

344034, г. Ростов-на-Дону, ул. Загорская, д. 23, к. А, офис 1

105/42, Bolshaya Sadovaya st., Rostov-on-Don, 344006;

23A, Zagorskaya st., Rostov-on-Don, 344034

Южный федеральный университетРоссияSouthern Federal UniversityRussian FederationЮжный федеральный университет; Медицинский центр «Наука»РоссияSouthern Federal University; Medical Center “Nauka”Russian FederationМедицинский центр «Наука»; Ростовский государственный медицинский университетРоссияMedical Center “Nauka”; Rostov State Medical UniversityRussian Federation2024130720242344553Copyright © Ид М.А., Александрова А.А., Затонский С.А., Гутникова Л.В., Шкурат Т.П., 20242024Ид М.А., Александрова А.А., Затонский С.А., Гутникова Л.В., Шкурат Т.П.Eid M.A., Aleksandrova A.A., Zatonsky S.A., Gutnikova L.V., Shkurat T.P.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/2462

Введение. Коронавирусное заболевание 2019 (COVID-19) – высококонтагиозное заболевание, вызываемое коронавирусом SARSCoV-2. Несколько факторов риска восприимчивости и тяжести COVID-19 связаны с окислительным стрессом. Целью настоящего исследования было изучение ассоциации однонуклеотидных полиморфизмов (SNP) генов глутатион S-трансферазы pi-1 (GSTP1) и глутатионпероксидазы 4 (GPx4) с тяжестью заболевания COVID-19.Методы. Пациенты были разделены на две группы в зависимости от тяжести симптомов. Для генотипирования использовалась аллель-специфическая полимеразная цепная реакция в реальном времени (RT-PCR). Для исследования межгенных взаимодействий проводился MDR-анализ (multifactor dimensionality reduction).Результаты. Показана значимая ассоциация GPX4 rs713041 с тяжестью течения COVID-19 (p=0,035). У большинства носителей генотипа GPX4 718 (TT) было тяжелое течение COVID-19 (ОШ=3,50; 95% ДИ [1,18-10,35]). Трехлокусная модель взаимодействия SNP-SNP была статистически значимой (p = 0,0084, ОШ = 2,42; 95% ДИ [1,24–4,73]). Анализ неравновесия по сцеплению GSTP1 rs1695 и rs1138272 показал высокую вероятность неравновесия по сцеплению между двумя сайтами (D’ = 0,949).Выводы. Насколько нам известно, это первое исследование ассоциаций и межгенных взаимодействий GSTP1 rs1695, GSTP1 rs1138272 и GPX4 rs713041 с тяжестью симптомов COVID-19. Полученные результаты могут служить новым потенциальным фактором прогноза COVID-19.

Background. Coronavirus disease 2019 (COVID-19) is a highly contagious disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several risk factors of COVID-19 susceptibility and severity are associated with oxidative stress.Aim: to investigate the association of single nucleotide polymorphisms (SNPs) of glutathione S-transferase pi-1 (GSTP1) and glutathione peroxidase 4 (GPX4) genes with the severity of COVID-19.Methods. Study subjects were divided into two groups based on the severity of their symptoms. Allele-specific real time polymerase chain reaction (RT-PCR) was used for genotyping, and multifactor dimensionality reduction (MDR) analysis was performed to investigate the SNP-SNP interaction models.Results. The results showed a significant association of GPX4 rs713041 with the severity of COVID-19 (p=0.035). Most of GPX4 718TT carriers had a severe course of COVID-19 (OR=3.50; 95% CI [1.18-10.35]). The resulted three-locus SNP-SNP interaction model was statistically significant (p=0.0084, OR = 2.42; 95% CI [1.24 - 4.73]). Linkage disequilibrium analysis of GSTP1 SNPs rs1695 and rs1138272 showed a high possibility of linkage disequilibrium between the two sites (D’ = 0.949).Conclusions: To our knowledge, this is the first study to investigate the association of GSTP1 rs1695, GSTP1 rs1138272, and GPX4 rs713041 and SNP-SNP interaction with the severity of COVID-19 symptoms. The obtained results may serve as a novel potential factor of COVID-19 prognosis.

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