medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLC10.25557/2073-7998.2021.10.25-32medgen-1984Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHСвязь локуса 17q23.1 с клинически выраженным атеросклерозом сонных артерийThe association of 17q23.1 locus with advanced carotid atherosclerosisГончароваИ. А.GoncharovaI. A.irina.goncharova@medgenetics.ruКоролеваЮ. А.KorolevaIu. A.noemail@neicon.ruСлепцовА. А.SleptsovA. A.noemail@neicon.ruБабушкинаН. П.BabushkinaN. P.noemail@neicon.ruКузнецовМ. С.KuznetsovM. S.noemail@neicon.ruКозловБ. Н.KozlovB. N.noemail@neicon.ruНазаренкоМ. С.NazarenkoM. S.noemail@neicon.ruНаучно-исследовательский институт медицинской генетики, Томский национальный исследовательский медицинский центр Российской академии наукРоссияResearch Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of SciencesRussian FederationНаучно-исследовательский институт кардиологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCardiology Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesRussian Federation20212112202120102532Copyright © Гончарова И.А., Королева Ю.А., Слепцов А.А., Бабушкина Н.П., Кузнецов М.С., Козлов Б.Н., Назаренко М.С., 20212021Гончарова И.А., Королева Ю.А., Слепцов А.А., Бабушкина Н.П., Кузнецов М.С., Козлов Б.Н., Назаренко М.С.Goncharova I.A., Koroleva I.A., Sleptsov A.A., Babushkina N.P., Kuznetsov M.S., Kozlov B.N., Nazarenko M.S.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/1984

Проведен анализ ассоциаций rs8078424 (chr17:59873104) с риском развития клинически выраженного атеросклероза сонных артерий и патогенетически значимыми для развития данной патологии количественными признаками, а также оценена связь данного генетического варианта с экспрессией гена MIR21 в лейкоцитах периферической крови пациентов. В группу обследования включены пациенты с клинически выраженным атеросклерозом сонных артерий (стеноз при ультразвуковом исследовании более 80%; n=104). В качестве контроля использованы популяционная выборка жителей г. Томска (n=161) и группа, состоящая из относительно здоровых индивидов, которые имели начальные стадии атеросклероза сонных артерий, но без гемодинамически значимых изменений (стеноз не более 24%; n=84). Генотипирование rs8078424 выполняли методом MALDI-TOF масс-спектрометрии на приборе Sequenom MassARRAY® (США). Уровень экспрессии гена MIR21 в лейкоцитах крови оценивался методом капельной цифровой ПЦР на приборе QX200 Droplet Digital PCR System (Bio-Rad). Выявлено, что генотип GG rs8078424 является протективным относительно развития клинически выраженного атеросклероза сонных артерий (OR=0,023, 95%CI:0,08-0,62; р=0,003), ассоциирован с меньшим уровнем общего холестерина в сыворотке крови и повышенной экспрессией гена MIR21 в лейкоцитах крови пациентов. Потенциальными молекулярными механизмами ассоциации rs8078424 с атеросклерозом являются изменение сайта связывания транскрипционных факторов (FOXP1, SOX18, GATA3, HOXD9, HOXD10 и C/EBPalpha), а также связь с экспрессией гена MIR21 в клетках органов-мишеней патологии. Полиморфизм локуса 17q23.1 (в области генов TUBD1, VMP1/MIR21) представляет интерес для более детального изучения подверженности к сердечно-сосудистым заболеваниям в контексте эпигенетических механизмов в отдельных клетках органов-мишеней патологии.

In this study, we analyzed the association of rs8078424 (chr17:59873104) with the risk of advanced carotid atherosclerosis and disease-related traits. We also assessed the association of this genetic variant with the expression of MIR21 gene in peripheral blood leukocytes of patients. Methods. A group of cases included patients with advanced carotid atherosclerosis who had artery stenosis with 80% or more by ultrasound examination (n=104). We used two control groups. Resident population of Tomsk was the first group (n=161). A second group consists of relatively healthy individuals who had non-hemodynamically significant carotid atherosclerosis (24% or less; n=84). Genotyping of rs8078424 was performed using MALDI-TOF mass spectrometry on a Sequenom MassARRAY® (USA) platform. The expression level of the MIR21 gene in peripheral blood leukocytes was assessed by droplet digital PCR on a QX200 Droplet Digital PCR System (Bio-Rad). Results. The GG rs8078424 genotype was found to be protective against of advanced carotid atherosclerosis (OR=0.023, 95%CI:0.08-0.62; p=0.003) and associated with a lower level of total cholesterol in the serum and increased MIR21 gene expression in peripheral blood leukocytes of the patients. Potential molecular mechanisms of the association of rs8078424 with atherosclerosis include alteration of transcription factors binding sites (FOXP1, SOX18, GATA3, HOXD9, HOXD10, and C/EBPalpha) as well as relationship with the MIR21 gene expression in cells of target organs. Conclusion. The polymorphism of the 17q23.1 locus (in the region of the TUBD1, VMP1/MIR21 genes) is of interest for a more detailed study of susceptibility to cardiovascular diseases in the context of epigenetic mechanisms in single cells of the target organs.

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