Saule Rakhimova

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide and is the principal cause of death in low- and middle-income countries. Although cardiovascular outcome trials have established the benefits of Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) in reducing major adverse cardiovascular events, the translation of this evidence into routine clinical practice in Central Asia remains limited and underexplored. Specifically, in Kazakhstan, despite measurable improvements in cardiac infrastructure over the past decade, critical gaps persist in early diagnosis, cardiometabolic risk stratification, and the integration of newer pharmacological strategies into routine practice. In this review, we aim to evaluate the potential role of GLP-1-based therapies within the current cardiovascular prevention landscape in Kazakhstan. It also synthesizes current mechanistic evidence and findings from major clinical trials supporting the use of GLP-1RAs as cardiometabolic agents with potential cardiovascular benefits. Furthermore, we examine the practical factors that may influence their adoption within Kazakhstan’s health system, including accessibility, affordability, clinician preparedness, prescribing capacity, regulatory considerations, and policy integration. By integrating evidence from cardiovascular outcome trials, clinical studies, and health-system perspectives, this review seeks to provide a balanced assessment of the potential contribution of GLP-1-based therapies to cardiovascular risk reduction in Kazakhstan while identifying priorities for future research, implementation strategies, and health policy development.

Background/Objectives: Genetic factors are known to influence overall immune vulnerability to diseases, such as tuberculosis (TB); however, isolating the genetic component can be challenging as social and environmental causes, such as smoking, alcohol consumption, and unemployment, also drive disease risk. To reduce heterogeneity related to these factors, we performed a targeted immunogenetic association study of TB susceptibility in a Kazakh case–control cohort selected among individuals without the typical socioeconomic and nutritional risk factors linked to TB. Methods: We performed genotyping using an immune-focused targeted array; after quality control at sample and variant level, removal of ancestry-based outliers, and adjustment for population stratification, the final dataset included 164 participants (84 cases, 80 controls) and 181,595 variants. We performed four complementary analyses: single-variant association testing using logistic regression with Firth correction where required adjusted for sex and genetic ancestry, gene-based aggregation testing, functional annotation, and polygenic risk scoring using existing multi-ancestry TB genetic resources. Results: While no variant reached formal significance, the top nominal signal, rs1560036 (OR = 2.98, p = 2.4 × 10⁻⁵), lies within CPLX2, which ranked among the top genes in gene-based analysis, a result driven largely by the same variant. A nominally associated variant in the classical MHC region, rs9263600, is separately reported in GTEx as a cis-eQTL for HLA-B and HLA-C. Similarly, polygenic risk scores showed directionally consistent but statistically non-significant associations with case status (Asia-base AUC = 0.560; Europe-base AUC = 0.537). Conclusions: Although our study was not adequately powered to detect small-to-moderate genetic effects, it offers an important perspective on TB genetics in a population underrepresented in existing research. These findings provide an openly available dataset and candidate signals for replication in larger, independent cohorts.

Cardiometabolic disorders, including obesity, insulin resistance and type 2 diabetes mellitus, remain major biomedical problems closely linked to vascular complications. Dipeptidyl peptidase-4 (DPP-4) is a clinically validated therapeutic target because inhibition of this enzyme prolongs the activity of incretin hormones and supports glucose-dependent insulin secretion. This review compiles and critically evaluates plant-derived DPP-4 inhibitors, with emphasis on chemical class, enzyme source, quantitative activity, assay interpretability, and the translational relevance of reported findings. The available literature indicates that flavonoids and polyphenolic compounds dominate the field, although assay heterogeneity, medium effects, potential aggregation, and insufficient selectivity data limit interpretation. Among natural scaffolds, chalcones and aurones, including lanceoletin, leptosidin, xanthoangelol, chalconaringenin 2′-O-β-D-glucopyranoside, and aureusidin 6-O-β-D-glucopyranoside, represent comparatively well-supported lead-like scaffolds that warrant further standardized evaluation. The evidence does not support using plant-derived DPP-4 inhibitors as substitutes for approved antidiabetic drugs. Their greatest value lies in expanding chemical space and providing lead-like scaffolds for standardized potency, selectivity, kinetic and preclinical validation.

Introduction. Cardiovascular diseases remain one of the leading causes of mortality worldwide. Endothelial dysfunction, inflammation, and lipid metabolism disorders play a key role in their pathogenesis and may be influenced by genetic factors. Aim: To investigate the association between polymorphisms in the APOE, eNOS, ALOX, and MTHFR genes and the risk of cardiovascular disease. Materials and methods. The study included 40 patients diagnosed with dilated cardiomyopathy and ventricular tachycardia and 52 apparently healthy individuals forming the control group. Genotyping of gene polymorphisms was performed using polymerase chain reaction with restriction fragment analysis and direct sequencing. Results. Among the genetic variants investigated, statistically significant associations with disease susceptibility were identified for the MTHFRrs1801133, MTHFR rs1801131 polymorphisms. In this cohort, the C/C genotype of MTHFR rs1801131 was associated with an increased disease risk. In addition, MTHFR rs1801133 demonstrated a significant association with disease susceptibility under codominant, dominant, and overdominant inheritance models. No statistically significant associations were observed for the remaining polymorphisms (APOE rs429358, APOErs7412, eNOS rs2070744, ALOX15 rs2619112, and rs7612186). Conclusion. The findings of this study suggest that MTHFRrs1801133, MTHFR rs1801131 polymorphisms may contribute to susceptibility to dilated cardiomyopathy with ventricular tachycardia in this cohort, whereas no evidence of association was found for the investigated APOE, eNOS and ALOX15 variants. Given the limited sample size, these findings should be interpreted with caution and require validation in larger, independent studies. Введение. Сердечно-сосудистые заболевания остаются одной из ведущих причин смертности во всём мире. Существенную роль в их патогенезе играют эндотелиальная дисфункция, воспалительные процессы и нарушения липидного обмена, которые могут быть обусловлены генетическими факторами. Цель исследования. Исследовать связь между полиморфизмами генов APOE, eNOS, ALOX и MTHFR и риском сердечно-сосудистых заболеваний. Материалы и методы. В исследование были включены 40 пациентов с дилатационной кардиомиопатией и желудочковой тахикардией и 52 практически здоровых человека контрольной группы. Генотипирование полиморфизмов генов проводилось методом полимеразной цепной реакции с последующим анализом рестрикционных фрагментов и прямым секвенированием. Результаты. Среди исследованных генетических вариантов были выявлены статистически значимые ассоциации с предрасположенностью к заболеваниям для полиморфизмов MTHFR rs1801133 и MTHFR rs1801131. В этой когорте генотип C/C полиморфизма MTHFR rs1801131 был ассоциирован с повышенным риском заболевания. Кроме того, MTHFR rs1801133 продемонстрировал значимую ассоциацию с предрасположенностью к заболеваниям при кодоминантном, доминантном и сверхдоминантном типах наследования. Для остальных полиморфизмов (APOE rs429358, APOE rs7412, eNOS rs2070744, ALOX15 rs2619112 и rs7612186) статистически значимых ассоциаций не наблюдалось. Заключение. Результаты данного исследования позволяют предположить, что полиморфизмы MTHFR rs1801133 и MTHFR rs1801131 могут способствовать предрасположенности к дилатационной кардиомиопатии с желудочковой тахикардией в данной когорте, в то время как для исследованных вариантов APOE, eNOS и ALOX15 никаких доказательств ассоциации обнаружено не было. Учитывая ограниченный размер выборки, эти результаты следует интерпретировать с осторожностью и требуют подтверждения в более крупных независимых исследованиях. Кіріспе. Жүрек-қантамыр аурулары әлем бойынша өлім-жітімнің негізгі себептерінің бірі болып табылады. Олардың патогенезінде эндотелий дисфункциясы, қабыну процестері және липидтік алмасудың бұзылыстары маңызды рөл атқарады. Бұл өзгерістер генетикалық факторлармен байланысты болуы мүмкін. Зерттеу мақсаты. APOE, eNOS, ALOXжәне MTHFR гендерінің полиморфизмдері мен жүрек-қантамыр ауруларының даму қаупі арасындағы байланысты зерттеу және олардың эндотелий дисфункциясы, қабыну және липидтік...

Introduction: Obesity contributes to adverse cardiometabolic changes and may promote left ventricular hypertrophy (LVH), but evidence from Central Asian populations remains limited. Objective: To evaluate the association between body mass index (BMI) and LVH and assess the discriminative ability of BMI for LVH among Kazakh women with clinically diagnosed atherosclerosis. Methods: This cross-sectional study included 153 unrelated Kazakh women aged ≥30 years with clinically diagnosed atherosclerosis. Participants were stratified by BMI into normal weight, overweight and obesity groups. Biochemical and medical data were compared between groups using Kruskal-Wallis and chi-square tests. Binary logistic regression with adjustment and receiver operating characteristic analysis were performed to assess the association between BMI and LVH. Results: Across BMI categories, triglycerides, fasting glucose, HbA1c and C-reactive protein increased significantly, while HDL-C declined. The prevalence of LVH increased from 17.2% in normal-weight women to 45.2% in obese women. Higher BMI was associated with increased odds of LVH in unadjusted analysis and persisted after adjustments. BMI alone showed modest discrimination for LVH (AUC 0.675), which improved when combined with metabolic and hypertension covariates (AUC 0.754). Conclusion: Among Kazakh women with atherosclerosis, BMI remained associated with LVH and a less favourable cardiometabolic profile. BMI functions most effectively as a risk marker when combined with established cardiovascular risk factors rather than as a standalone predictor. Введение: Ожирение способствует неблагоприятным кардиометаболическим изменениям и может приводить к развитию гипертрофии левого желудочка (ГЛЖ), однако данные о населении Центральной Азии остаются ограниченными. Цель: Оценить связь между индексом массы тела (ИМТ) и ГЛЖ, а также дискриминационную способность ИМТ в отношении выявления ГЛЖ у казахских женщин с клинически диагностированным атеросклерозом. Методы: В данное поперечное исследование были включены 153 неродственные казахские женщины в возрасте ≥30 лет с клинически диагностированным атеросклерозом. Участницы были распределены в группы с нормальной массой тела, избыточной массой тела и ожирением в зависимости от ИМТ. Клинические и биохимические характеристики сравнивали с использованием критерия Краскела–Уоллиса, критерия χ² Пирсона или точного критерия Фишера. Для оценки связи между ИМТ и ГЛЖ, а также дискриминационной способности ИМТ применяли бинарную логистическую регрессию и анализ ROC-кривых. В регрессионный анализ были включены 148 участниц с полными данными. Результаты: По мере увеличения категории ИМТ отмечалось значимое повышение уровней триглицеридов, глюкозы натощак, HbA1c и С-реактивного белка, тогда как уровень холестерина липопротеинов высокой плотности снижался. Распространённость ГЛЖ увеличилась с 17,2% у женщин с нормальной массой тела до 45,2% у женщин с ожирением. Более высокий ИМТ был связан с увеличением шансов наличия ГЛЖ, и данная связь сохранялась после поправки на возраст, степень артериальной гипертензии, функцию почек и метаболические факторы (ОШ на увеличение ИМТ на 1 кг/м² — 1,08; 95% ДИ: 1,00–1,17; p=0,041). ИМТ отдельно продемонстрировал умеренную дискриминационную способность в отношении ГЛЖ (AUC 0,675), которая повысилась при включении ИМТ в модель вместе с клиническими и метаболическими показателями (AUC 0,754). Заключение: У казахских женщин с атеросклерозом более высокий ИМТ был связан с ГЛЖ и менее благоприятным кардиометаболическим профилем. ИМТ может использоваться как простой маркер сердечно-сосудистого риска в сочетании с установленными клиническими и метаболическими факторами риска, однако его дискриминационная способность как самостоятельного маркера ограничена. Кіріспе: Семіздік қолайсыз кардиометаболикалық өзгерістерге ықпал етеді және сол жақ қарынша гипертрофиясының (СҚГ) дамуына әкелуі мүмкін, бірақ Орталық Азия халқы туралы деректер шектеулі болып қала...

Introduction. Elite athletes undergo regular high-intensity training to maintain fitness and improve performance. Training overload is necessary to achieve significant results. However, failure to balance training and recovery can lead to overtraining syndrome. To prevent this, regular monitoring of biochemical markers is required to assess the body's adaptive processes. Aim of the study. Comparative analysis of blood biochemical parameters in Olympic athletes of Kazakhstan to assess training load effects and prevent overtraining syndrome Methods. A biochemical analysis was conducted to measure levels of creatinine, creatine kinase (CK), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in Olympic athletes. Results. Significant differences in biochemical markers were observed among sports disciplines. Creatinine (p<0.001), alkaline phosphatase (p<0.001), AST (p<0.001), CK (p=0.008), and LDH (p<0.001) levels differed significantly between groups, whereas ALT showed no significant variation (p=0.191). Post hoc analyses revealed higher creatinine levels in weightlifters and freestyle wrestlers, elevated alkaline phosphatase levels in combat sport athletes, and significant sport-specific differences in AST, CK, and LDH, reflecting variations in muscle metabolism and training-related physiological adaptation. Conclusion. These findings underscore the importance of monitoring biochemical markers in elite athletes to prevent overtraining and optimize the training process. Keywords: biochemical markers, sports medicine, creatine kinase, lactate dehydrogenase, athletes of Kazakhstan.

Background: Pediatric epilepsy is a clinically and genetically heterogeneous group of disorders, particularly in early-onset and syndromic presentations. Data integrating molecular findings with detailed clinical phenotyping remain limited in Kazakhstan and Central Asia. Methods: We conducted a retrospective, single-center, clinically selected, referral-based case series study of 31 pediatric patients evaluated at a tertiary center in Kazakhstan for epilepsy or epilepsy-associated neurodevelopmental disorders and found to have clinically relevant or potentially relevant genetic findings. Clinical records were reviewed for demographics, age at seizure onset, seizure semiology, developmental profile, EEG, MRI, extra-neurological features, treatment response, and family history. Variants were interpreted using ACMG-based criteria, and inheritance/segregation data were incorporated where available. Results: The cohort included 15 males and 16 females. Median seizure onset was 5.0 months (IQR 2.0–13.0), and 22/31 patients (71.0%) presented within the first year of life. Developmental delay/intellectual impairment was observed in 20/31 cases (64.5%), speech delay in 17/31 (54.8%), motor delay in 15/31 (48.4%), and hypotonia in 12/31 (38.7%). Variants were identified in 23 genes, including several variants with limited or no prior support in ClinVar or peer-reviewed reports. Ion channelopathies were the largest mechanistic group (12/31, 38.7%), followed by mitochondrial/metabolic disorders (6/31, 19.4%), mTOR pathway disorders (5/31, 16.1%), and neurodevelopmental/chromatin/transcriptional disorders (4/31, 12.9%). SCN1A was the most recurrent gene (8/31, 25.8%) and showed a broad phenotypic continuum from Dravet-compatible to non-Dravet presentations. EEG and MRI abnormalities were common and often syndromic in pattern. Treatment response was frequently partial or poor, although selected genotype-linked treatment observations were noted in PRRT2 (carbamazepine), PNPO (pyridoxine), and one SCN1A case (stiripentol). Conclusions: This study expands the clinicogenetic characterization of pediatric epilepsy cases with clinically relevant or potentially relevant genetic findings in Kazakhstan and highlights the value of integrated molecular, phenotypic, and segregation analysis in underrepresented populations.

Introduction. Circulating tumor DNA (ctDNA) has emerged as a valuable biomarker for non-invasive cancer diagnostics and treatment monitoring. However, pre-analytical variables, including blood collection and sample processing, significantly influence ctDNA yield and analytical reliability. Optimizing these conditions is crucial for ensuring reproducible and accurate ctDNA measurements. Aim. To perform a comparative evaluation of blood collection tubes and DNA extraction methods for the isolation of circulating tumor DNA from the blood plasma of patients with oncological diseases. Materials and Methods. Plasma samples were collected using two types of blood collection tubes: PaxGene and Streck. ctDNA was extracted using three different systems: Raissol, MagMax, and QiaAmp. Quantitative performance, reproducibility, and variability of ctDNA yield were assessed across all combinations of collection tubes and extraction methods. Statistical analysis was performed to evaluate differences among extraction systems. Discussion. The results demonstrated that QiaAmp consistently provided higher ctDNA concentrations across both collection systems. Samples collected in PaxGene tubes exhibited lower variability and improved analytical stability compared with Streck tubes. Statistically significant differences among extraction methods were observed for PaxGene samples, while increased variability in Streck samples limited the ability to discriminate between methods. These findings emphasize the critical role of pre-analytical optimization in ctDNA workflows and support the implementation of standardized protocols to improve reliability in liquid biopsy analysis. Conclusion. The results demonstrate that both blood collection tubes and the DNA extraction method significantly affect ctDNA recovery, highlighting the importance of optimizing and standardizing pre-analytical workflows for reliable liquid biopsy analysis. Введение. Циркулирующая опухолевая ДНК (ctDNA) стала ценным биомаркером для неинвазивной диагностики рака и мониторинга терапии. Однако преданалитические переменные, включая сбор крови и обработку образцов, существенно влияют на выход ctDNA и надежность анализа. Оптимизация этих условий необходима для обеспечения воспроизводимости и точности измерений ctDNA. Цель. Целью данного исследования было проведение сравнительной оценки эффективности пробирок для сбора крови и методов экстракции ДНК при выделении циркулирующей опухолевой ДНК из плазмы крови пациентов с онкологическими заболеваниями. Материалы и методы. Плазменные образцы были собраны с использованием двух типов пробирок: PaxGene и Streck. Экстракция ctDNA проводилась с использованием трех систем: Raissol, MagMax и QiaAmp. Оценивались количественные показатели, воспроизводимость и вариабельность выхода ctDNA для всех комбинаций пробирок и методов экстракции. Для оценки различий между методами экстракции проводился статистический анализ. Обсуждение. Результаты показали, что система QiaAmp стабильно обеспечивала более высокие концентрации ctDNA при использовании обеих пробирок. Образцы, собранные в пробирки PaxGene, продемонстрировали меньшую вариабельность и улучшенную аналитическую стабильность по сравнению с пробирками Streck. Статистически значимые различия между методами экстракции наблюдались для образцов PaxGene, тогда как повышенная вариабельность в образцах Streck ограничивала возможность различия методов. Эти данные подчеркивают критическую роль оптимизации преданалитических условий и поддерживают внедрение стандартизированных протоколов для повышения надежности анализа жидкостной биопсии. Заключение. Полученные результаты показывают, что как тип пробирок для сбора крови, так и используемые методы экстракции ДНК существенно влияют на выход циркулирующей опухолевой ДНК, что подчёркивает необходимость оптимизации и стандартизации преданалитических этапов для надёжного анализа жидкостной биопсии. Кіріспе. Циркуляциялық қатерлі ісік ДНҚ (ctDNA) ракты инвазивті емес диагностикалау және емдеу мониторингі үшін маңызды биомаркерге айналды. Алайда, қан жинау және үлгілерді өңдеу сияқты алдын ала аналитикалық факторлар ctDNA шығымына және...

Background/Objectives: Cardiac arrhythmias are among the leading causes of sudden cardiac death (SCD). Pathogenic variants in potassium channel genes play a key role in inherited arrhythmia syndromes, yet their contribution in Central Asian populations remains poorly characterized. Methods: We performed targeted next-generation sequencing (NGS) using a 96-gene custom Haloplex panel in 79 Kazakhstani patients with clinically diagnosed arrhythmias, including atrioventricular block, sick sinus syndrome, and atrial fibrillation. Detected variants in potassium channel genes were classified according to ACMG guidelines and correlated with clinical phenotypes. Results: A total of 52 variants were identified across 11 potassium channel genes. Two likely pathogenic variants (KCNH2 p.Cys66Gly and p.Arg176Trp) and six variants of uncertain significance (VUS) in KCNQ1, KCNE2, KCNE3, and KCNJ8 were detected. Two novel previously unreported variants were found in KCNE5 and KCND3. Patients harboring pathogenic variants commonly presented with early-onset arrhythmias or a positive family history of cardiovascular disease. Carriers of KCNH2 variants exhibited mild QT prolongation and recurrent syncope. Conclusions: This is the first genetic study of potassium channel gene mutations in Kazakhstani patients with cardiac arrhythmias. The detection of pathogenic and novel variants highlights the clinical utility of integrating genetic testing into diagnostic and management pathways for arrhythmia syndromes. Population-specific genomic data are essential for improving risk stratification, guiding medication safety, and enabling cascade family screening in Central Asia.