👤 Makhabbat Bekbossynova

Familial Hypercholesterolemia is a hereditary metabolic disorder characterized by elevated low-density lipoprotein cholesterol, as high as 1 in 250 individuals, leading to cardiovascular diseases like atherosclerosis. It's caused by autosomal dominant mutations in genes LDL receptor, Apolipoprotein B-100, and proprotein convertase subtilisin/kexin type 9 (PCSK9), FH leads to lifelong elevation of LDL-C. Carotid atherosclerosis, a sign of systemic atherosclerosis, can be studied as a clinical feature of FH, providing insights into its risk assessment, early diagnosis, and intervention. To determine contribution of specific genetic variants to carotid atherosclerosis, thereby improving our understanding of the genetic basis of cardiovascular risk in FH. A search was performed through PubMed, Google Scholar, Medline and Scopus databases using the preselected terms. Studies were selected and reviewed based on inclusion and exclusion criteria by two authors independently, with third-party adjudication. Total of 9 trials were included: 4 cross-sectional studies, 4 retrospective cohorts and 1 prospective cohort studies. Total sample size of all reviewed studies was 3,033 in different settings. Studies revealed higher cIMT levels in FH patients and showed significant association of LDLR mutations with severe atherosclerosis. APOB and PCSK9 mutations in this study had limited effect on cIMT levels and prevalence of carotid plaques. This review highlights the essential role of LDLR mutations in progression of carotid artery atherosclerosis among patients with FH. Incorporating information on FH mutations into risk assessment for atherosclerosis patients can help predict disease progression and cardiovascular outcomes more effectively. Show less

Ventricular tachycardia (VT) is a major cause of sudden cardiac death (SCD). Clinical investigations can sometimes fail to identify the underlying cause of VT and the event is classified as idiopathic (iVT). VT contributes significantly to the morbidity and mortality in patients with coronary artery disease (CAD) and dilated cardiomyopathy (DCM). Since mutations in arrhythmia-associated genes frequently determine arrhythmia susceptibility screening for disease-predisposing variants could improve VT diagnostics and prevent SCD in patients. Ninety-two patients diagnosed with coronary heart disease (CHD), DCM, or iVT were included in our study. We evaluated genetic profiles and variants in known cardiac risk genes by targeted next generation sequencing (NGS) using a newly designed custom panel of 96 genes. We hypothesized that shared morphological and phenotypical features among these subgroups may have an overlapping molecular base. To our knowledge, this was the first study of the deep sequencing of 96 targeted cardiac genes in Kazakhstan. The clinical significance of the sequence variants was interpreted according to the guidelines developed by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) in 2015. The ClinVar and Varsome databases were used to determine the variant classifications. Targeted sequencing and stepwise filtering of the annotated variants identified a total of 307 unique variants in 74 genes, totally 456 variants in the overall study group. We found 168 mutations listed in the Human Genome Mutation Database (HGMD) and another 256 rare/unique variants with elevated pathogenic potential. There was a predominance of high- to intermediate pathogenicity variants in In this study we showed that in patients with VT secondary to coronary artery disease, DCM, or idiopathic etiology multiple rare mutations and clinically significant sequence variants in classic cardiac risk genes associated with cardiac channelopathies and cardiomyopathies were found in a similar pattern and at a comparable frequency. Show less