vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2023-20-2-95-105vestim-907Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEСвязь полиморфных вариантов генов NPPB rs198389 и NPPA rs5068 с уровнем натрийуретических пептидов и прогрессированием сердечной недостаточности у пациентов с фибрилляцией предсердийAssociation of NPPB rs198389 and NPPA rs5068 single-nucleotide polymorphisms with natriuretic peptide levels and heart failure progression risks in patients with atrial fibrillationhttps://orcid.org/0000-0002-4890-2092МатюкевичМ. Ч.MatsiukevichM. Ch.

Матюкевич Марина Чеславовна – аспирант

ул. Горького, 80, 230009, г. Гродно

Marina Ch. Matsiukevich – Postgraduate student

80, Gorky Str., 230009, Grodno

marinamat0305@gmail.comhttps://orcid.org/0000-0002-1706-1243СнежицкийВ. А.SnezhitskiyV. A.

Снежицкий Виктор Александрович – член-корреспондент, д-р мед. наук, профессор

ул. Горького, 80, 230009, г. Гродно

Victor A. Snezhitskiy – Corresponding Member

80, Gorky Str., 230009, Grodno

https://orcid.org/0000-0002-3337-4231СтепуроТ. Л.StepuroT. L.

Степуро Татьяна Леонидовна – канд. биол. наук

ул. Горького, 80, 230009, г. Гродно

 Tatsiana L. Stepuro – Ph. D. (Biol.)

80, Gorky Str., 230009, Grodno

tatianastepuro31@gmail.comГродненский государственный медицинский университетGrodno State Medical University20230506202320295105Copyright © Матюкевич М.Ч., Снежицкий В.А., Степуро Т.Л., 20232023Матюкевич М.Ч., Снежицкий В.А., Степуро Т.Л.Matsiukevich M.C., Snezhitskiy V.A., Stepuro T.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/907

Натрийуретические пептиды (НУП) являются сильнейшими предикторами неблагоприятного исхода у пациентов с сердечной недостаточностью (СН). Однонуклеотидные полиморфные варианты (Single Nucleotide Polymorphysms (SNPs) rs198389 гена NPPB и rs5068 гена NPPA ассоциированы с измененными уровнями НУП. Однако не определена роль SNPs генов-кандидатов в активности системы НУП у лиц с СН и фибрилляцией предсердий (ФП), а также не установлена связь ассоциации SNPs NPPA/NPPB с риском возникновения сердечно-сосудистых заболеваний у пациентов данной группы.

Целью исследования было установить распределение частот аллелей и генотипов SNPs rs5068 NPPA и rs198389 NPPB в селективной выборке белорусской популяции, определить связь данных SNPs с концентрацией компо нентов системы НУП, а также оценить прогностическую значимость данных SNPs в отношении риска госпитализации по причине прогрессирования СН у пациентов с СН и постоянной формой ФП.

В исследовании приняли участие 187 пациентов. В основную группу были включены 152 пациента с СН и фракцией выброса левого желудочка (ФВ ЛЖ) < 50 %. В группу 1 вошли 48 пациентов с СН и ФП, в группу 2 – 51 пациент с СН и синусовым ритмом (СР), в контрольную группу – 35 человек. Определены уровни предсердного и мозгового натрийуретических пептидов (ANP и BNP) и N-терминального фрагмента мозгового натрийуретического пептида (NT-proBNP). Проведено генетическое тестирование полиморфных локусов rs5068 гена NPPA и rs198389 гена NPPB. Первичной конечной точкой в исследовании определена госпитализация по причине прогрессирования СН.

Средний период наблюдения составил 12,1 [от 9 до 14] мес. Распределение частот генотипов и аллелей SNPs rs198389 NPPB и rs5068 NPPA у пациентов с СН с ФВ ЛЖ < 50 % сопоставимо с таковым у лиц, не страдающих сердечнососудистыми заболеваниями. У пациентов с СН и ФВ ЛЖ < 50 % и постоянной формой ФП минорный аллель C rs198389 NPPB ассоциирован с более высоким уровнем BNP, чем у пациентов с СН и СР (542 [333,7; 909,4] пг/мл против 247,3 [244; 365,2] пг/мл; р < 0,05), но при этом не зависит от уровня NT-proBNP. У пациентов с СН и постоянной формой ФП уровень ANP не ассоциирован с rs5068 NPPA. Частота встречаемости аллеля Т rs198389 NPPB у госпитализированных пациентов была значимо ниже, чем у лиц, которые не были госпитализированы (22 (44 %) пациента против 83 (62 %); p = 0,04). Присутствие в генотипе аллеля С rs198389 NPPB ассоциировано с более высоким риском прогрессирования СН у пациентов с СН и ФП (отношение шансов = 2,071 [95 % ДИ – 1,072…4,001]; р < 0,05).

Natriuretic peptides (NUPs) are the strongest predictors of poor prognosis in patients with heart failure (HF). Single-nucleotide polymorphisms (SNPs) rs198389 of the NPPB gene and rs5068 of the NPPA gene are associated with altered levels of NUP. The role of candidate gene polymorphisms in the activity of the NUP system and the association of NPPA/ NPPB SNPs with the risk of cardiovascular disease (CVD) in individuals with HF and atrial fibrillation (AF) is not well understood.

The study aims to evaluate the allele and genotype frequencies of NPPA rs5068 and NPPB rs198389 SNPs in a selective sample of the Belarusian population, to determine the relationship of these SNPs with NUP concentrations, and to assess the prognostic significance of these SNPs on the risk of HF hospitalization in patients with HF and permanent AF.

The study involved 187 patients. The main group included 152 patients with HF with left ventricular ejection fraction (LVEF) < 50 %. Group 1 included 48 patients with HF and AF; group 2 – 51 patients with HF and sinus rhythm (SR) and 35 patients in the control group. The levels of atrial and brain natriuretic peptides (ANP and BNP) and the N-terminal fragment of the brain natriuretic peptide (NT-proBNP) were determined. A genetic testing of polymorphic loci of the rs5068 NPPA gene and the rs198389 NPPB gene was performed. The primary endpoint of the study was hospitalization due to HF progression.

The average observation period was 12.1 [from 9 to 14] months. The distribution of the genotype and allele frequencies of rs198389 NPPB and rs5068 NPPA in HF patients with LVEF < 50 % is comparable to that in individuals without CVD. In patients with HF and persistent AF, the minor allele C rs198389 NPPB is associated with higher BNP levels compared to patients with HF and SR (542 [333.7; 909.4] pg/ml versus 247.3 [244; 365.2] pg/ml; p < 0.05), but it has no relationship with the NT-proBNP level. In patients with HF and permanent AF, the ANP levels are not associated with rs5068 NPPA.

The frequency of the T allele rs198389 NPPB in hospitalized patients was significantly lower compared to patients who were not hospitalized (22 patients (44 %) versus 83 patients (62 %); p = 0.04). The presence of the C allele rs198389 NPPB was associated with a higher risk of HF progression in patients with HF and AF, the odds ratio (OR) = 2.071 [95 % CI from 1.072 to 4.001], p < 0.05.

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