Many genetic variants associated with metabolic disorders have incomplete penetrance in human. Their phenotypic manifestation depends on the life style factors. In this work, we compared the associations of genotypes at 11 polymorphic sites with body mass index (BMI) and lipid metabolism parameters (levels of total cholesterol (TC), triglycerides, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C)) in three groups of adolescents from Novosibirsk, examined in 1999, 2009 and 2019. In each group, from 187 to 665 persons were genotyped at each site. One-way analysis of variance (independent covariates: gender and age) was used for evaluation. For rs1800497 in the ANKK1 gene, rs53576 in the OXTR gene, rs1360780 in the FKBP5 gene, and rs4680 in the COMT gene, as well as for tandem repeats in the promoter of the MAOA gene, promoter and intron 2 of the SLC6A4 gene (separately and as part of a haplotype), and 3′-untranslated region of the SLC6A3 no associations of genotypes with BMI and lipid metabolism parameters were found in any of the groups. For APOE genotype, an association was obtained with TC levels: p = 0.042 and 0.034, respectively, in the 1999 and 2009 collection groups, as well as with LDL-C: p = 0.001 and 0.002, respectively, in the 2009 and 2019 groups. Moreover, the maximum levels of TC and LDL-C were found among carriers of most common genotype ε3ε3 in 1999 group, and among carriers of atherogenic allele ε4 in other two groups. Thus, it was shown that in adolescents there was an opposite correlation of carriage of the ε4ε4 genotype for the APOE gene with the levels of total cholesterol and LDL cholesterol in the case of normal and reduced calorie intake. For rs6265 in the BDNF gene, the level of statistical significance of the association of the common C allele with TC and LDL-C levels was directly correlated with dietary caloric intake ( p = 0.617 and 0.573; p = 0.049 and 0.090; p = 0.010 and 0.024, respectively, in the groups of 1999, 2009 and 2019).

Aim. Present two clinical cases of Maturity-Onset Diabetes of the Young, which is based on the presence of pathogenic variants in the glucokinase (GCK) gene — GCK-MODY; to characterize behavioral and cardiometabolic risk factors for diabetes complications. Key points. In the first clinical case, the pathogenic variant p.Trp257Ter (c.770G>A, NM_000162.5) of the GCK gene, previously described in the literature, was identified in the proband and his father, in the second — the pathogenic variant p.Cys271Ter (c.1113C>A, NM_000162. 5) GCK gene. Probands are young men, 22 and 21 years old, respectively. They were first diagnosed with diabetes in the ages of 10 and 6 years during routine examinations. There were no clinical symptoms of hyperglycemia; they did not take and do not currently take hypoglycemic drugs. When examined 11 and 15 years after the diagnosis of diabetes, in each patient the level of C-peptide was within the reference values, which indicates the preservation of the secretory function of pancreatic β-cells. Antibodies were negative, the level of glycated hemoglobin (HbA1c) was 5.7 and 6.1%, respectively. No complications of diabetes were identified in either patient. The fathers of probands from both families had HbA1c levels of 6.4 and 6.5%, respectively. The father of the proband from the first clinical case does not comply with recommendations for a healthy lifestyle and nutrition, and does not deny weekly alcohol consumption. Upon examination, he was found to be overweight, arterial hypertension, dyslipidemia, steatohepatitis, and atherosclerosis of the brachiocephalic vessels, which increase the risk of cardiovascular events. The father of the proband from the second clinical case follows recommendations for a healthy lifestyle. During the examination, body weight, blood pressure, blood lipids are within the target range. Conclusion. Presenting two clinical cases and family histories of patients with GCK-MODY, the authors note that the compliance with the principles of a healthy lifestyle, assessment and correction of the main risk factors will help avoid the emergence and progression of complications in patients with GCK-MODY. When monitoring and treating patients with diabetes of any type, it is important to follow the principles of preventive medicine. Keywords: Molecular genetic research, GCK gene, monogenic diabetes mellitus, Maturity-Onset Diabetes of the Young, hyperglycemia, diabetes mellitus in young people.

A relevant task for the healthcare system is to identify the groups most predisposed to cardiovascular diseases (CVD) of atherosclerotic genesis. Risk stratification is an important component of choosing a management strategy for both CVD patients and those with risk factors. The individual risk of an unfavorable cardiovascular outcome is determined by genetic factors in addition to lifestyle factors. The aim of the work was to examine the association of variants of the APOE, CETP and chromosomal region 9p21.3 with coronary heart disease (CHD), myocardial infarction (MI) and acute heart failure (ACF) in a sample of residents of Novosibirsk. Material and methods. Sample: 2516 participants of the HAPIEE project (57.5 ± 0.2 years old, male to female ratio 45:55). The choice of the variants of the APOE, CETP and the chromosomal region 9p21.3 was due to their significant association with CVD according to several studies and meta-analyses. Genotyping of rs708272, rs429358 and rs7412 was performed by Real-Time PCR using TaqMan reagents; genotyping of rs1333049 was performed using a commercial KASP kit. Results. Allele C of rs1333049 was associated with an increased risk of CHD, MI and AHF in the subgroup of men (p = 0,008) and in the general group (p = 0,002). In the general group, the incidence of CHD, MI and AHF was significantly lower in carriers of the G allele (odds ratio 0.748, 95 % confidence interval 0.606–0.924, p = 0.007). We confirmed the association of the ɛ2/ɛ4 genotype of the APOE gene with CHD, MI and AHF among males (p = 0.007) and in the whole study sample (p = 0.009). In the women subgroup the genotype ɛ2/ɛ2 (p < 0.0001) was associated with CHD, MI and AHF, while in carriers of the genotype ɛ3/ɛ3, the incidence of CHD, MI and AHF was significantly lower (odds ratio 0.675, 95 % confidence interval 0.509–0.894, p = 0,006). Conclusions. This work shows the association of rs1333049 of chromosomal region 9p21.3 and rs429358&rs7412 of the APOE gene with the risk of CHD, MI and AHF in a sample of residents of Novosibirsk. These variants may be recommended for inclusion into a genetic risk score.

Нарушение липидного обмена – один из главных факторов риска развития атеросклероза у человека. В ходе полногеномных исследований ассоциаций выявлены десятки генов, варианты которых ответственны за предрасположенность к дислипидемиям. Однако многие из ассоциаций либо не подтверждаются при репликации, либо оказываются специфичными для отдельных популяций. Целью данной работы была оценка распространенности одного из наиболее плейотропных полиморфизмов генома человека – rs13107325 – в популяционной выборке подростков г. Новосибирска и анализ его ассоциации с показателями липидного обмена. В работе использовались образцы крови и данные обследования 1582 подростков, собранные в ходе стандартизированного медицинского обследования в НИИ терапии и профилактической медицины – филиале Института цитологии и генетики СО РАН. Генотипирование по rs13107325 гена SLC39A8 выполнено при помощи ПЦР в режиме реального времени, для оценки корреляции генотипов с показателями липидного обмена использовали однофакторный дисперсионный анализ. Установлено, что частота аллеля Т варианта rs13107325 (p = 0,05 ± 0,004) в европеоидной выборке Западной Сибири ниже наблюдаемой в европейских популяциях. Ассоциация с показателями липидного обмена (содержанием в сыворотке крови общего холестерина, триглицеридов и холестерина липопротеинов высокой плотности), а также индексом массы тела не обнаружена ни в целом, ни в какой-либо из групп, различавшихся периодами отбора проб и контрастными по среднему уровню потребления пищи. Данный факт может говорить о том, что вклад варианта rs13107325 в дислипидемии у подростков Западной Сибири незначителен, и средние показатели потребления пищи не влияют на пенетрантность rs13107325 в отношении нарушения липидного обмена и индекса массы тела.

Understanding the molecular mechanisms of atherosclerotic vascular lesions formation is necessary both for assessing the risks of cardiovascular diseases and for finding approaches to their therapy. The task remains relevant, despite the large number of studies carried out, because there are differences in the factors of genetic predisposition to atherosclerosis and its complications between different ethno-territorial groups. The aim of this study was to search for genetic variants of pattern recognition receptors associated with lipid metabolism disorders that can lead to the development of coronary atherosclerosis (CA).Material and methods. Analysis of exons and adjacent splicing sites of pattern recognition receptors genes in patients with CA (30 men), and then genotyping of a population sample from Novosibirsk (n = 1441) by real-time PCR for selected rs113706342 of the TLR1 gene and analysis of associations of its carriage with lipid metabolism were performed.Results and discussion. The frequency of the minor allele rs113706342 C of the TLR1 gene in the sample of residents of Novosibirsk was 0.0114 ± 0.0062, the carriage of this variant was associated with an increased level of low-density lipoprotein cholesterol in both women and men (p = 0.009 and p = 0.019, respectively). Women carriers of the minor allele C for rs113706342 also had a statistically significant increase in total serum cholesterol (p = 0.013) compared with TT homozygotes. To test the role of this variant in the development of CA, genotyping of an extended sample of patients is required. In one of the patients with CA, a previously undescribed single nucleotide variant chr16:3614637 G/C was found, leading to the Leu101Val substitution in the NLRC3 gene; segregation analysis is required to assess its functional significance.Conclusions. The association of rs113706342 C of the TLR1 gene with lipid metabolism disorders in the Russian population is shown.

One of the most common congenital metabolic disorders is familial hypercholesterolemia. Familial hyper-cholesterolemia is a condition caused by a type of genetic defect leading to a decreased rate of removal of low-density lipoproteins from the bloodstream and a pronounced increase in the blood level of total cholesterol. This disease leads to the early development of cardiovascular diseases of atherosclerotic etiology. Familial hypercholesterolemia is a monogenic disease that is predominantly autosomal dominant. Rare pathogenic variants in the LDLR gene are present in 75–85 % of cases with an identified molecular genetic cause of the disease, and variants in other genes (APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, and others) occur at a frequency of < 5 % in this group of patients. A negative result of genetic screening for pathogenic variants in genes of the low-density lipoprotein receptor and its ligands does not rule out a diagnosis of familial hypercholesterolemia. In 20–40 % of cases, molecular genetic testing fails to detect changes in the above genes. The aim of this work was to search for new genes associated with the familial hypercholesterolemia phenotype by modern high-tech methods of sequencing and machine learning. On the basis of a group of patients with familial hypercholesterolemia (enrolled according to the Dutch Lipid Clinic Network Criteria and including cases confirmed by molecular genetic analysis), decision trees were constructed, which made it possible to identify cases in the study population that require additional molecular genetic analysis. Five probands were identified as having the severest familial hypercholesterolemia without pathogenic variants in the studied genes and were analyzed by whole-genome sequencing on the HiSeq 1500 platform (Illumina). The whole-genome sequencing revealed rare variants in three out of five analyzed patients: a heterozygous variant (rs760657350) located in a splicing acceptor site in the PLD1 gene (c.2430-1G>A), a previously undescribed single-nucleotide deletion in the SIDT1 gene [c.2426del (p.Leu809CysfsTer2)], new missense variant c.10313C>G (p.Pro3438Arg) in the LRP1B gene, and single-nucleotide deletion variant rs753876598 [c.165del (p.Ser56AlafsTer11)] in the CETP gene. All these variants were found for the first time in patients with a clinical diagnosis of familial hypercholesterolemia. Variants were identified that may influence the formation of the familial hypercholesterolemia phenotype.

Моногенные нарушения – патологии, которые вызваны изменениями только одного гена. Одним из наиболее распространенных (1:250) моногенных нарушений липидного обмена является семейная гиперхолестеринемия (СГХС) [1]. СГХС приводит к раннему развитию сердечно-сосудистых заболеваний (ССЗ) атеросклеротического генеза [2–4]. Редкие патогенные варианты в гене LDLR определяются в 80–85 % случаев, когда выявлена молекулярно-генетическая причина развития СГХС, варианты в других генах определяются с частотой менее 5 % (APOB, PCSK9, LDLRAP1, ABCG5, ABCG8 и др.) [5, 6]. У лиц с СГХС риск развития ССЗ в 2,5–10 раз выше по сравнению с контрольной группой [7, 8], но в случае диагностики и лечения СГХС в раннем возрасте риск значительно снижается (≈ 80 %) [7]. Активное выявление пациентов с СГХС и применение каскадного скрининга могут помочь обеспечить лечение до начала клинических проявлений ССЗ [9].

The goal of the study was exploring the range of variants of the PRL, PRLR, and PRLHR genes in women of reproductive age with nontumor hyperprolactinemia. In women with hyperprolactinemia of nontumor origin (n = 15) targeted high throughput sequencing of PRL, PRLR, and PRLHR genes was performed. The targeted panel of genes included coding regions and adjacent splicing sites. Analysis of the PRL, PRLR, and PRLHR genes revealed a number of rare and common variants. In the PRL gene, the common variant rs1205955 was identified (MAF А = 0.279). For the PRLR gene, the rare variant rs185353023 was identified in the 3'UTR (MAF A/C = 0.003) and 12 common variants were detected. For the PRLHR gene, ten common variants were identified. The maximum number of variants was localized in the 3'UTR region and introns. For the first time in Russia, targeted high throughput sequencing of the PRL, PRLR, and PRLHR genes was performed, according to the results of which no obvious pathological variants were revealed in the studied genes in women with an increased content of nonneoplastic prolactin. The discovered polymorphism in these genes allows further study of its association with impaired function of the prolactin component of hormonal regulation.

Hyperlipidemia is one of the most common metabolic disorders in humans, leading to the atheros clerosis. It is known that lipid metabolism disorders can be associated with genetic predisposition. However, even in patients with clinically confirmed familial hypercholesterolemia, its genetic cause remains unknown in 30 % of cases. The search for genetic variants associated with primary hyperlipidemias is a promising direction in the development of diagnostics and personalized medicine. Aim of the study was to assess of the association of polymorphic sites rs3813627, rs3135506 and rs3785617 of the apolipoprotein genes APOA2 , APOA5 and APOH , respectively, with lipid metabolism and atherogenic index in the population of Novosibirsk. Material and methods. Genotyping by polymerase chain reaction followed by analysis of restriction fragment length polymorphism at the rs3813627, rs3135506 and rs3785617 of the APOA2 , APOA5 and APOH genes, respectively, was carried out in 522 people from 9360 a random population sample of Novosibirsk and in 266 people from the same sample with a total cholesterol content more than 300 mg/dl. A one-way ANOVA of the association of genetic variants with serum lipid levels and atherogenicity index was performed. Results. The allele frequencies of all studied polymorphic sites in the Novosibirsk population differed from those previously identified among Europeans. A significant increase ( p = 0.02) in average total cholesterol content in AA – AG – GG genotype series for rs3785617 of the APOH was revealed. The frequency of the CC genotype for the rs3135506 of the APOA5 in the group with total cholesterol contentration exceeding 300 mg/dl was lower compared to the control group ( p = 0.038, odds ratio 0.66, 95 % confidence interval 0.46–0.97). For rs3813627, there were no differences in genotype frequencies and in lipid metabolism. Conclusions. The rs3135506 and rs3785617 can modify the hyperlipidemia phenotype among the Caucasoid population of Western Siberia.

В одной трети случаев причина внезапной смерти остается необъясненной после проведения стандартного судебно-медицинского исследования. При отрицательной аутопсии во многих странах рекомендовано проведение посмертного молекулярно-генетического исследования. Цель исследования – оценить диагностическую значимость молекулярной аутопсии методом экзомного секвенирования для мужчин молодого возраста, умерших внезапной сердечной смертью (ВСС). Материал и методы . Выполнено экзомное секвенирование ДНК группы молодых мужчин (37 человек), умерших ВСС в возрасте до 45 лет (средний возраст 32,4 ± 6,4 года). ДНК выделена методом фенол-хлороформной экстракции из ткани миокарда. Экзомный анализ выполнен на платформе Illumina. Для некоторых из выявленных вариантов проведено подтверждающее прямое автоматическое секвенирование по Сэнгеру. Результаты . Из 37 образцов ДНК при анализе результатов секвенирования 205 генов обнаружено более 30 вариантов в 17 образцах (46 %), вероятно имеющих отношение к фенотипу ВСС. Найденные мутации локализованы в генах, ассоциированных с фенотипами, приводящими к развитию ВСС ( дилатационная или гипертрофическая кардиомиопатия, нарушения ритма сердца). Заключение. Впервые в России проведено экзомное секвенирование образцов ДНК мужчин, умерших ВСС в возрасте до 45 лет. Молекулярная аутопсия методом экзомного секвенирования – эффективный метод поиска причинных вариантов нуклеотидной последовательности при ВСС.

ЧАСТОТА САХАРНОГО ДИАБЕТА ТИПА MODY В СИБИРСКОМ РЕГИОНЕ

Aim. The goal of the study was to analyze the differential expression of lipid metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis.Material and Methods. The study was performed on the specimens of atherosclerotic plaques in 45–65-year-old patients with coronary atherosclerosis with stable exertional angina functional class II-IV without acute coronary syndrome. Coronary atherosclerosis was verified by coronary angiography. Atherosclerotic plaque tissue was sampled intraoperatively when indicated. Whole-genome sequencing of ribonucleic acid (RNA) was performed using the TruSeq RNA Sample Preparation Kit (Illumina, USA).Results. We analyzed the differences in the expression of 12 genes including LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, ABCA1, APOA1, APOE, LPL, SCARB1, and SREBF2 depending on the type of atherosclerotic plaques. The expression level of APOE gene was eight times higher in unstable atherosclerotic plaques of dystrophic-necrotic type (p < 0.0001). The expression levels of LDLR and APOB genes were eight times higher in stable atherosclerotic plaques (p < 0.0001). We did not find differences in the expression levels of the ABCG5, ABCG8, APOC3, CETP, CLPS, CYP7A1, and PNPLA5 genes.Conclusion. The study showed the differences in the activity of individual metabolism-related genes in the atherosclerotic plaques of different types in patients with coronary atherosclerosis. Obtained data may become the basis for the development of test systems aimed at predicting the development of atherosclerotic process and its complications.

1 Федеральное государственное бюджетное научное учреждение «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук» 630090, Россия, г. Новосибирск, просп. Академика Лаврентьева, 10 2 Научно-исследовательский институт терапии и профилактической медицины – филиал Федерального государственного бюджетного научного учреждения «Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наук» 630089, Россия, г. Новосибирск, ул. Бориса Богаткова, 175/1

Highlights. Probably causal mutations of QT interval prolongation in genes associated with LQTS were found in men of the Siberian population.Aim. To detect and study mutations in individuals with borderline prolongation of the QT interval in Siberian males.Methods. The study was conducted on the material of the international project HAPIEE in the period from 2003 to 2005 and screening of young people aged 25–44, performed in Novosibirsk. The total sample of men was 1353 people aged 25 to 69 years. From each age subgroup (25–29, 30–34, ..., 65–69 years old) 2–3 samples with the highest QT values were selected . The study group consisted of 30 men who subsequently underwent sequencing of a panel of genes. The search for mutations was carried out in genes associated with long QT syndrome (LQTS): KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2, CACNA1, SCN4B, KCNJ5, ANK2, CAV3, SNTA1, AKAP9, CALM1 and CALM2. All identified single nucleotide variants were verified by direct Sanger sequencing.Results. Three rare variants in the LQTS genes have been identified: p.P197L of the KCNQ1 gene, p.R176W, and p.D1003GfsX116 of the KCNH2 gene.Conclusion. In Caucasian men from the Novosibirsk population with borderline prolongation of the QT interval, probably causal substitutions in the LQTS genes – KCNH2 and KCNQ1, contributing to the prolongation of the QT interval, were found. To clarify the spectrum and frequency of occurrence of various mutations in genes, life-threatening arrhythmias in the population, additional studies are needed on extended samples.

Purpose of the study. To determine the frequency of the rs9536314 (F325V) polymorphism of the KL gene and the association of this variant with a number of biochemical and anthropometric parameters in men of the study group and in the Caucasian population of Western Siberia. Materials  and methods. The study group (69 men, average age 61.2 ±11.5 years) was randomly formed  from a sample of persons who applied to the clinic and polyclinic of NIITPM - a branch of the ICG SB RAS and GBUZ NSO Hospital of war veterans No. 3 (178 men, aged 50-65 years old and over 80 years old). The population group was randomly selected (219 people) from the sample surveyed within the framework of the International Multicenter Project "Risk Factors for Cardiovascular Diseases in Eastern Europe" HAPIEE (9360 participants, 45–69 years old, mean age 53.8±7 years old, Caucasians > 90 %). Biochemical parameters were determined by standard enzymatic methods. Serum concentration of Klotho protein was measured by ELISA. Genomic DNA was amplified by polymerase chain reaction in a standard reaction mixture and further digested with TaqI B restriction enzyme. Results. The frequency of genotypes (TT, TG, and GG) and alleles (T and G) rs9536314 of the KL gene in the study group corresponds to the data in the population of Western Siberia, as well as the population of Western and Eastern Europe. There were no statistically significant differences in the mean values of the studied clinical and biochemical parameters depending on the rs9536314 genotypes of the KL gene in the study group and in the population. In the study group, the level of Klotho protein in the blood and the glomerular filtration rate in men with coronary heart disease and arterial hypertension did not differ in the autosomal dominant and autosomal recessive models for the rs9536314 KL gene. Conclusion . Thus, the frequency of the rs9536314 polymorphism of the KL gene in the study group corresponds to the frequency of the rs9536314 polymorphism of the KL gene in the Caucasian population of Western Siberia. Biochemical and anthropometric parameters, as well as the Klotho protein, do not have statistically significant differences depending on the genotypes of rs9536314 of the KL gene in the examined men.

Factor V, encoded by the F5 gene, is a procoagulant blood clotting factor that increases the production of thrombin, the central enzyme that converts fibrinogen to fibrin, which leads to the formation of a blood clot. The F5 gene is localized to 1q24.2 chromosome and consists of 25 exons. There are various mutations in the F5 gene that lead to resistance of activated protein C (APC) (elimination of the APС cleavage site in factor V and factor Va), which can lead to arterial and venous thrombosis. The aim of the present study was to analyze variants of the F5 gene in patients diagnosed with coronary atherosclerosis without acute coronary syndrome with stable functional class II–IV angina pectoris, confirmed by coronary angiography data, using the method of whole exome sequencing. Material and methods . The study was conducted in the framework of the Program of joint research work IIPM — branch of the ICG SB RAS and the FSBI «Research Institute of Circulation Pathology named after E.N. Meshalkin» Ministry of Health of Russian Federation. The study included 30 men aged 40–70 years with coronary angiography-­verified coronary atherosclerosis, without ACS, with stable angina pectoris of the II–IV FC. Patients were admitted for coronary bypass surgery, and endarteriaectomy from the coronary artery (s) was performed during the operation according to intraoperative indications. Whole exome sequencing (SureSelectXT Human All Exon v.6+UTR) was carried out on an Illumina NextSeq 500 instrument (USA). Results. In 30 patients, 29 single-­nucleotide variants were found in the F5 gene. In patients with coronary atherosclerosis, rs9332701 of the F5 gene is 3.33 times more common, and rs6027 is 1.67 times more common than in the population. And rs184663825 was found in 3.33% of cases, while its occurrence in the population is 0.05%. For variants rs6034 and rs144979314, a possible damaging effect on the protein product is shown. Conclusion . The single-­nucleotide variants rs9332701, rs6027, rs184663825, rs6034, rs144979314 of the F5 gene are of interest for inclusion in the genetic panels for the analysis of risk factors for the development of acute coronary syndrome.

Factor V, encoded by the F5 gene, is a procoagulant blood clotting factor that increases the production of thrombin, the central enzyme that converts fibrinogen to fibrin, which leads to the formation of a blood clot. The F5 gene is localized to 1q24.2 chromosome and consists of 25 exons. There are various mutations in the F5 gene that lead to resistance of activated protein C (APC) (elimination of the APС cleavage site in factor V and factor Va), which can lead to arterial and venous thrombosis. The aim of the present study was to analyze variants of the F5 gene in patients diagnosed with coronary atherosclerosis without acute coronary syndrome with stable functional class II–IV angina pectoris, confirmed by coronary angiography data, using the method of whole exome sequencing.Material and methods. The study was conducted in the framework of the Program of joint research work IIPM — branch of the ICG SB RAS and the FSBI «Research Institute of Circulation Pathology named after E.N. Meshalkin» Ministry of Health of Russian Federation. The study included 30 men aged 40–70 years with coronary angiography-­verified coronary atherosclerosis, without ACS, with stable angina pectoris of the II–IV FC. Patients were admitted for coronary bypass surgery, and endarteriaectomy from the coronary artery (s) was performed during the operation according to intraoperative indications. Whole exome sequencing (SureSelectXT Human All Exon v.6+UTR) was carried out on an Illumina NextSeq 500 instrument (USA).Results. In 30 patients, 29 single-­nucleotide variants were found in the F5 gene. In patients with coronary atherosclerosis, rs9332701 of the F5 gene is 3.33 times more common, and rs6027 is 1.67 times more common than in the population. And rs184663825 was found in 3.33% of cases, while its occurrence in the population is 0.05%. For variants rs6034 and rs144979314, a possible damaging effect on the protein product is shown.Conclusion. The single-­nucleotide variants rs9332701, rs6027, rs184663825, rs6034, rs144979314 of the F5 gene are of interest for inclusion in the genetic panels for the analysis of risk factors for the development of acute coronary syndrome.