Type 2 diabetes (T2D) and obesity are common chronic disorders with multifactorial etiology. In our study, we performed an exome sequencing analysis of 110 patients of Russian ethnicity together with a multi-perspective approach based on biologically meaningful filtering criteria to detect novel candidate variants and loci for T2D and obesity. We have identified several known single nucleotide polymorphisms (SNPs) as markers for obesity (rs11960429), T2D (rs9379084, rs1126930), and body mass index (BMI) (rs11553746, rs1956549 and rs7195386) (p < 0.05). We show that a method based on scoring of case-specific variants together with selection of protein-altering variants can allow for the interrogation of novel and known candidate markers of T2D and obesity in small samples. Using this method, we identified rs328 in LPL (p = 0.023), rs11863726 in HBQ1 (p = 8 × 10⁻⁵), rs112984085 in VAV3 (p = 4.8 × 10⁻⁴) for T2D and obesity, rs6271 in DBH (p = 0.043), rs62618693 in QSER1 (p = 0.021), rs61758785 in RAD51B (p = 1.7 × 10⁻⁴), rs34042554 in PCDHA1 (p = 1 × 10⁻⁴), and rs144183813 in PLEKHA5 (p = 1.7 × 10⁻⁴) for obesity; and rs9379084 in RREB1 (p = 0.042), rs2233984 in C6orf15 (p = 0.030), rs61737764 in ITGB6 (p = 0.035), rs17801742 in COL2A1 (p = 8.5 × 10⁻⁵), and rs685523 in ADAMTS13 (p = 1 × 10⁻⁶) for T2D as important susceptibility loci in Russian population. Our results demonstrate the effectiveness of whole exome sequencing (WES) technologies for searching for novel markers of multifactorial diseases in cohorts of limited size in poorly studied populations.

Aim. To analyze the structure of clinical data, as well as the principles of collecting and storing related data of the biobank of the National Medical Research Center for Therapy and Preventive Medicine (hereinafter Biobank).Material and methods. The analysis was carried out using the documentation available in the Biobank, as well as the databases used in its work. The paper presents clinical data on biosamples available in the Biobank as of August 18, 2021.Results. At the time of analysis, the Biobank had 373547 samples collected from 54192 patients within 37 research projects. The article presents the analysis of data representation and quantitative assessment of the presence/absence of common diagnoses in clinical projects. Approaches to documenting clinical information associated with biological samples stored in the Biobank were assessed. The methods and tools used for standardization and automation of processes used in the Biobank were substantiated.Conclusion. The Biobank of the National Medical Research Center for Therapy and Preventive Medicine is the largest research biobank in Russia, which meets all modern international requirements and is one of the key structures that improve the research quality and intensify their conduct both within the one center and in cooperation with other biobanks and scientific institutions. The collection and systematic storage of clinical abstracts of biological samples is an integral and most important part of the Biobank’s work.

The National Medical Research Center for Preventive Medicine of Russia (NMRCPM) conducts epidemiological and clinical research for the development of personalized medicine. This is why NMRCPM has f...

Cystic fibrosis, phenylketonuria, alpha-1 antitrypsin deficiency, and sensorineural hearing loss are among the most common autosomal recessive diseases, which require carrier screening. The evaluation of population allele frequencies (AF) of pathogenic variants in genes associated with these conditions and the choice of the best genotyping method are the necessary steps toward development and practical implementation of carrier-screening programs. We performed custom panel genotyping of 3821 unrelated participants from two Russian population representative samples and three patient groups using real-time polymerase chain reaction (PCR) and next generation sequencing (NGS). The custom panel included 115 known pathogenic variants in the CFTR, PAH, SERPINA1, and GJB2 genes. Overall, 38 variants were detected. The comparison of genotyping platforms revealed the following advantages of real-time PCR: relatively low cost, simple genotyping data analysis, and easier detection of large indels, while NGS showed better accuracy of variants identification and capability for detection of additional pathogenic variants in adjacent regions. A total of 23 variants had significant differences in estimated AF comparing with non-Finnish Europeans from gnomAD. This study provides new AF data for variants associated with the studied disorders and the comparison of genotyping methods for carrier screening.

Current prophylactic actions prevent or significantly delay the majority of cardiovascular diseases (CVD). Various factors are interconnected and affect a person throughout his life, determining the risk of CVD. This indicates the need for preventive measures at all stages of life and even before birth. The beneficial effects of CVD prevention are realized through various genetic, epigenetic and metabolic mechanisms. Due to the fact that many risk factors for CVD have a cumulative effect, the introduction of preventive measures from the earliest life stages will be most effective. The purpose of the article is to consider various aspects of CVD prevention in the preconceptional, prenatal and infant periods.

ЦЕЛЬ ИССЛЕДОВАНИЯ Оценить комплаентность пациентов с гетерозиготной семейной гиперхолестеринемией (геСГХС) в течение 5-летнего периода работы регистра РЕНЕССАНС (Регистр пациентов с СГХС и пациентов очень высокого сЕрдечно-Сосудистого риска с недоСтАточной эффективНоСтью, проводимой гиполипидемической терапии). МАТЕРИАЛ И МЕТОДЫ РЕНЕССАНС является открытым, национальным, наблюдательным исследованием и включает больных с СГХС. Проводилась оценка факторов риска атеросклероза, анамнеза сердечно-сосудистых заболеваний (ССЗ), интенсивности гиполипидемической терапии (ГЛТ). Каждому пациенту определены уровни общего холестерина, триглицеридов, холестерина липопротеидов высокой плотности в сыворотке крови. Содержание холестерина липопротеидов низкой плотности (ХС ЛНП) рассчитывали по формуле Фридвальда. РЕЗУЛЬТАТЫ В исследование включено 2317 пациентов с геСГХС, из которых 58% — женщин. При включении в регистр 59% больных относились к категории высокого сердечно-сосудистого риска. Динамический визит проведен у 47% пациентов, период наблюдения составил 24 [11; 42] мес. Больные с динамическим визитом чаще имели определенный диагноз геСГХС и отягощенный наследственный анамнез по ССЗ, были моложе и им в более раннем возрасте диагностировали СГХС (p<0,05). У пациентов без динамического визита были распространены модифицируемые факторы риска (p<0,001). Среди пациентов высокого сердечно-сосудистого риска 54% больных получали ГЛТ, очень высокого — 86%. За время наблюдения в регистре доля принимающих ГЛТ пациентов увеличилась с 59 до 78%, в том числе статинами в режиме высокой интенсивности с 36 до 54%, в комбинации с эзетимибом — с 15 до 34%, ингибиторами PCSK9 — с 4 до 14% (p<0,001 для всех). Целевого уровня ХС ЛНП достигли 13% пациентов. Данные симуляционного анализа продемонстрировали, что для адекватного контроля уровня ХС ЛНП, не менее 92,5% больных с геСГХС в регистре должны получать трехкомпонентную ГЛТ со статинами, эзетимибом и ингибиторами PCSK9. ЗАКЛЮЧЕНИЕ 5-летнее наблюдение за участниками регистра РЕНЕССАНС демонстрирует увеличение использования многокомпонентных схем лечения, но недостаточное для адекватного контроля ХС ЛНП.