Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC112010.15690/vramn1120CARDIOLOGY AND CARDIOVASCULAR SURGERY: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ КАРДИОЛОГИИ И СЕРДЕЧНО-СОСУДИСТОЙ ХИРУРГИИResearch ArticleGenetic aspects of lone atrial fibrillation in patients without structural heart diseaseГенетические аспекты развития идиопатической фибрилляции предсердий у больных без структурных сердечных аномалийhttps://orcid.org/0000-0002-6252-03229334-5672GolukhovaElena Z.ГолуховаЕлена Зеликовна
Russian Federation

MD, PhD, Professor

д.м.н., профессор, академик РАН

egolukhova@yahoo.comhttps://orcid.org/0000-0002-6918-70163348-5569ZholbaevaAygerim Z.ЖолбаеваАйгерим Замирбековна
Russian Federation
zamirbekkyzy@list.ruhttps://orcid.org/0000-0001-5089-01699161-9888ArakelyanMari G.АракелянМари Генриковна
Russian Federation
mariarakelyan@gmail.comhttps://orcid.org/0000-0002-5091-05188979-7098BulaevaNaida I.БулаеваНаида Ибадуллаевна
Russian Federation

MD, PhD

д.м.н.

naida_bulaeva@yahoo.comhttps://orcid.org/0000-0002-0726-75635693-0057MinashkinMichail M.МинашкинМихаил Михайлович
Russian Federation
mminashkin@gmail.comBakoulev Center for Cardiovascular Surgery RAMSНациональный медицинский исследовательский центр сердечно-сосудистой хирургии имени А.Н. БакулеваDiaem LtdООО «Диаэм»18092019051020197442452521004201903092019Copyright ©; 2019, "Paediatrician" Publishers LLCCopyright ©; 2019, Издательство "Педиатръ"2019"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/1120

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia. Among patients with AF the subgroup posessing AF without traditional risk factors is differentiated. Such patients are commonly referred as having “lone AF” and comprise 10–20% of all cases. A number of studies have demonstrated that the background of AF, and in particular lone AF, have a substantial genetic component.

Aims: To evaluate the influence of gene polymorphism to the development of atrial fibrillation in patients without concomitant valvular pathology and coronary artery disease.

Materials and methods: The study included 174 patients with atrial fibrillation and 124 controls without any cardiovascular pathology. All patients were divided into two subgroups: with “lone AF” (n=94) and with concomitant arterial hypertension (n=80). All patients underwent a complex of clinical, instrumental (ECG, echocardiography, computed tomography of the pulmonary veins) and laboratory tests (thyroid hormones, inflammatory markers, fibrosis), as well as genetic analysis (determination of single nucleotide polymorphisms described as AF risk factors in genes AGXT2, PDE4D, SLN, SCN5A, PITX2, PRRX1, ZFHX3, TBX5, CAV1 и HCN4).

Results: For the rare polymorphisms rs12291814 (SLN) and rs137854601 (SCN5A) wasn’t found anyone carrier of the minor allele (C and A, respectively). In the both patient subgroups the minor allele T of rs2200733 in PITX2 (OR=3.18, p<0.0001), minor allele G of rs3903239 in PRRX1, and minor alleles A of 2 polymorphisms rs2106261 and rs7193343 in ZFHX3 gene were revealed as risk factor of AF (OR=2.96, p<0.0001, OR=2.02, p=0.0045, OR=1.64, p=0.04, respectively). We also revealed significant difference between AF and control groups for rs3807989 in CAV1: homozygotic state of minor allele A has a protective effect on the development of arrhythmias (OR=0.39).

Conclusions: We revealed the association between the polymorphisms in genes regulating transcription and the development of atrial fibrillation. These polymorphisms have already described but their frequencies have never investigated in Russian population. But the polymorphisms influence to gene functions stays unclear, although attempts to investigate relationship between genotype and gene expression have been made. When the relationship will be discovered it can help us to modify our approach in treatment to patients with atrial fibrillation.

Обоснование. Фибрилляция предсердий — наиболее часто встречающаяся аритмия. Примерно в 10–20% случаев данное нарушение ритма сердца возникает у больных без сопутствующей кардиальной и экстракардиальной патологии. В этих случаях применяется термин «изолированная» или «идиопатическая фибрилляция предсердий». В значительной части случаев развития идиопатической фибрилляции предсердий предполагается роль генетических факторов. Наибольший интерес для изучения представляют случаи несемейной формы аритмии, обусловленные полиморфизмом генов, ответственных за кардиогенез и регулирующих активность других генов.

Цель исследования — определение роли ряда однонуклеотидных полиморфизмов в развитии идиопатической фибрилляции предсердий.

Методы. Обследованы 174 пациента с фибрилляцией предсердий и группа контроля в количестве 124 человек без сердечно-сосудистой патологии. Пациенты были разделены на две подгруппы — с изолированной формой фибрилляции предсердий (n=94) и с сопутствующей артериальной гипертензией (n=80). Всем пациентам проводился комплекс клинико-инструментальных (электро-, эхокардиография; компьютерная томография легочных вен) и лабораторных (гормоны щитовидной железы; маркеры воспаления, фиброза) исследований, а также выполнено генотипирование по полиморфным однонуклеотидным маркерам генов SLN (ген сарколипина), SCN5A (ген α-субъединицы потенциалзависимого натриевого канала типа V), PITX2 (ген парного гомеодомена 2), PRRX1 (ген парного гомеобокс-белка 1), ZFHX3 (ген цинково-пальцевого гомеобокс-белка), CAV (ген кавеолина).

Результаты. Для маркеров rs12291814 гена SLN и rs137854601 гена SCN5A не выявлено ни одного носителя минорного аллеля (соответственно С и А), что не противоречит литературным данным. Для полиморфных маркеров rs2200733 гена PITX2, rs3903239 гена PRRX1 и двух полиморфных маркеров rs2106261 и rs7193343 гена ZFHX3 минорный аллель является фактором риска аритмии для обеих подгрупп пациентов. Для полиморфного маркера rs3807989 гена, кодирующего кавеолин CAV1, выявлено статистически достоверное различие в частоте встречаемости минорного аллеля, при этом данный генотип оказывает протективное действие в отношении развития аритмии (OR=0,39).

Заключение. Полученные результаты показали взаимосвязь между полиморфными маркерами генов PITX2 (rs2200733; OR=3,18 p<0,0001), PRRX1 (rs3903239; OR=2,96, p<0,0001) и ZFHX3 (rs2106261; OR=2,02, p=0,045 и rs 7193343, OR=1,64, p=0,04), кодирующих факторы регуляции транскрипции, и развитием фибрилляции предсердий. Однако остаются открытыми вопросы, каким образом эти полиморфные маркеры влияют на функции генов и, соответственно, какой подход при коррекции состояния пациента с фибрилляцией предсердий будет наиболее эффективным.

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