Variants in the LDLR and the APOB genes in patients with familial hypercholesterolemia in the Republic of Sakha (Yakutia)

The aim of the study. Molecular genetic studies of familial hypercholesterolemia (FH) have been conducted in different regions of the Russian Federation for several decades. However, limited ethnic diversity in patient samples does not permit a comprehensive assessment of the full spectrum of gene variability responsible for FH development in the Russian population. The aim of this study was to characterize the molecular heterogeneity of the LDLR and APOB genes in patients with FH phenotype in the Republic of Sakha (Yakutia). Material and methods. A group of 48 patients with FH was enrolled at the Department of Lipid Disorders, Republican Clinical Hospital No. 3, Yakutsk. FH diagnosis was established using the Dutch Lipid Clinic Network (DLCN) Criteria. All patients underwent clinical examination, ultrasonographic evaluation, and blood sampling for biochemical and molecular genetic analyses. Molecular variants in index patients and segregation analysis in available family members were identified using direct automated Sanger sequencing of the LDLR gene promoter and all exons, as well as exon 26 of the APOB gene. Results. Pathogenic variants in the LDLR gene were identified in three index patients with the FH phenotype. Segregation analysis in families of index patients identified three additional carriers of the rs121908038 variant among first-degree relatives. Based on direct automated sequencing of exon 26 of the APO B gene, a pathogenic variant (rs5742904) was identified in one index patient and three of his first-degree relatives. Conclusions. Molecular genetic analysis of the LDLR gene and exon 26 of the APOB gene in patients with the FH phenotype from the Republic of Sakha (Yakutia) identified pathogenic variants in two genes. Heterozygous familial hypercholesterolemia was confirmed in index patients and segregated among first-degree relatives. These findings underscore the importance of genetic testing and family screening in FH diagnosis and management.