sibmedСибирский научный медицинский журналСибирский научный медицинский журнал2410-25122410-2520ИЦиГ СО РАН10.18699/SSMJ20240410sibmed-1617Research ArticleМЕДИКО-БИОЛОГИЧЕСКИЕ НАУКИBIOMEDICINEСвязь полиморфизма генов метаболизма витамина D с тяжестью поражения коронарного русла, оцененного по шкале SYNTAXAssociation of the vitamin D metabolism gene polymorphism with the severity of coronary lesions assessed by SYNTAX scorehttps://orcid.org/0000-0002-3002-2863ПонасенкоА. В.PonasenkoA. V.

Понасенко Анастасия Валериевна, к.м.н.

650002, г. Кемерово, б-р им. Академика Л.С. Барбараша, 6

Anastasia V. Ponasenko, candidate of medical sciences

650002, Kemerovo, Academician L.S. Barbarasha blvd., 6

ponaav@kemcardio.ruhttps://orcid.org/0000-0002-4467-8732СиницкаяА. В.SinitskayaA. V.

Синицкая Анна Викторовна, к.б.н.

650002, г. Кемерово, б-р им. Академика Л.С. Барбараша, 6

Anna V. Sinitskaya, candidate of biological sciences

650002, Kemerovo, Academician L.S. Barbarasha blvd., 6

cepoav1991@gmail.comhttps://orcid.org/0000-0002-4824-2418СиницкийМ. Ю.SinitskyM. Yu.

Синицкий Максим Юрьевич, к.б.н.

650002, г. Кемерово, б-р им. Академика Л.С. Барбараша, 6

Maxim Yu. Sinitsky, candidate of biological sciences

650002, Kemerovo, Academician L.S. Barbarasha blvd., 6

max-sinitsky@rambler.ruhttps://orcid.org/0000-0002-9714-4080ХуторнаяМ. В.KhutornayaM. K.

Хуторная Мария Владимировна

650002, г. Кемерово, б-р им. Академика Л.С. Барбараша, 6

Mariya V. Khutornaya

650002, Kemerovo, Academician L.S. Barbarasha blvd., 6

masha_hut@mail.ruhttps://orcid.org/0000-0003-4386-9489ДувановМ. К.DuvanovM. K.

Дуванов Максим Константинович

650002, г. Кемерово, б-р им. Академика Л.С. Барбараша, 6

Maxim K. Duvanov

650002, Kemerovo, Academician L.S. Barbarasha blvd., 6

duvamk@kemcardio.ruhttps://orcid.org/0000-0002-4642-3610БарбарашО. Л.BarbarashO. L.

Барбараш Ольга Леонидовна, д.м.н., акад. РАН

650002, г. Кемерово, б-р им. Академика Л.С. Барбараша, 6

Olga L. Barbarash, doctor of medical sciences, academician of the RAS

650002, Kemerovo, Academician L.S. Barbarasha blvd., 6

barbol@kemcardio.ruНИИ комплексных проблем сердечно-сосудистых заболеванийРоссияResearch Institute for Complex Issues of Cardiovascular DiseasesRussian Federation20242908202444496104Copyright © Понасенко А.В., Синицкая А.В., Синицкий М.Ю., Хуторная М.В., Дуванов М.К., Барбараш О.Л., 20242024Понасенко А.В., Синицкая А.В., Синицкий М.Ю., Хуторная М.В., Дуванов М.К., Барбараш О.Л.Ponasenko A.V., Sinitskaya A.V., Sinitsky M.Y., Khutornaya M.K., Duvanov M.K., Barbarash O.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://sibmed.elpub.ru/jour/article/view/1617

Целью данной работы стало определение связи между концентрациями сывороточных биомаркеров, полиморфизмом генов метаболизма витамина D и тяжестью поражения коронарного русла у пациентов со стабильной ИБС. Материал и методы. Обследовано 260 пациентов со стабильной ИБС, средний возраст которых составил 58 лет. Все участники исследования разделены на две группы по шкале SYNTAX: пациенты низкого риска с SYNTAX Score ≤ 31 (n = 224) и пациенты высокого риска с SYNTAX Score > 31 (n = 36). Для проведения иммуноферментного и генетического анализа кровь собирали из локтевой вены в вакуумные пробирки, содержащие активатор свертывания и K3-ЭДТА соответственно. Сывороточную концентрацию 25-гидроксивитамина D (DiaSource Diagnostics, Бельгия) и 1,25-дигидроксивитамина D (Immunodiagnostic Systems, Великобритания) определяли методом твердофазного ИФА в соответствии с протоколами производителей. Геномную ДНК выделяли методом фенол-хлороформной экстракции из цельной крови. Качество и количество выделенной ДНК оценивали на спектрофотометре NanoDrop (Thermo Fisher Scientific, США). Для анализа отобрано пять полиморфных вариантов двух генов: VDR (rs2228570 и rs73123) и GC (rs7041, rs1155563 и rs2298849). Генотипирование проводили методом ПЦР в режиме реального времени в 96-луночном планшете с флуоресцентно-меченными зондами TaqMan. Качество ПЦР контролировали повторным генотипированием 10 % образцов. Результаты. При анализе сывороточной концентрации исследуемых маркеров не показано статистически значимых различий у пациентов с разной выраженностью поражения коронарного русла. Выявлен один полиморфный вариант, ассоциированный с множественным поражением коронарного русла (rs2298849 GC) (отношение шансов 2,26, 95%-й доверительный интервал 1,28–3,99, p = 0,006) по аддитивной модели наследования. Кроме того, определено уменьшение концентрации 1,25-дигидроксивитамина D в сыворотке крови больных ИБС с множественным поражением коронарного сосудистого бассейна с генотипами A/A – A/G полиморфизма rs2228570 гена VDR и генотипами A/A rs7041 и А/А rs2298849 гена GC. Заключение. Аллельные варианты генов метаболизма витамина D ассоциированы со степенью поражения коронарных артерий, оцененной по шкале SYNTAX Score, у пациентов со стабильной ИБС. Сывороточная концентрация активной формы витамина D (1,25-дигидроксивитамина D) меньше у носителей гомозиготных генотипов по мажорным аллелям генов VDR и GC

This study aimed to determine the association of vitamin D serum blood levels and vitamin D gene polymorphism with the severity of coronary lesions in patients with stable coronary artery disease (CAD). Material and methods. 260 patients with stable CAD (average age was 58 years) were examined in the presented research. All patients were divided into two groups according to the SYNTAX score: low-risk patients with SYNTAX score ≤ 31 (n = 224) and high-risk patients with SYNTAX score > 31 (n = 36). For enzyme-linked immunosorbent assay and genetic analysis, peripheral blood was collected from the cubital vein into vacuum tubes containing coagulation activator and K3-EDTA, respectively. Serum blood level of 25-hydroxyvitamin D (DiaSource Diagnostics, Belgium) and 1,25-dihydroxyvitamin D (Immunodiagnostic Systems, Great Britain) were determined by enzyme-linked immunosorbent assay according to the manufacturers’ protocols. Genomic DNA was isolated by phenol-chloroform extraction method from whole blood. The quality and quantity of isolated DNA were assessed using NanoDrop spectrophotometer (Thermo Fisher Scientific, USA). Five polymorphic variants in the VDR (rs2228570 and rs73123) and GC (rs7041, rs1155563 and rs2298849) genes were selected for analysis. Genotyping was performed by real-time PCR in a 96-well plate with fluorescently labeled TaqMan probes. The quality of PCR was controlled by repeated genotyping of 10 % of the analyzed samples. Results. We found no statistically significant differences in serum blood level of the studied markers in patients from low-risk and high-risk groups. One polymorphic variant in the GC gene associated with the multiple coronary lesions (rs2298849) (odds ratio 2.26, 95 % confidence interval 1.28–3.99, p = 0.006) according to an additive inheritance model was identified. In addition, we determined the association between low serum blood level of 1,25-dihydroxyvitamin D in patients with CAD with multiple lesions of the coronary vascular system with A/A – A/G genotypes of the rs2228570 polymorphism in the VDR gene, A/A genotype of the rs7041 polymorphism and A/A genotype of the rs2298849 polymorphism in the GC gene. Conclusions. Allelic variants in the vitamin D metabolism genes are associated with the degree of coronary artery lesions assessed by the SYNTAX score in patients with stable CAD. Also, serum blood level of the active form of vitamin D (1,25-dihydroxyvitamin D) is less in carriers of homozygous genotypes for the major alleles of the VDR and GC genes.

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