MOLEKULARNA I BIOHEMIJSKA KARAKTERIZACIJA FAMILIJARNE HIPERHOLESTEROLEMIJE: POVEZANOST GENETSKIH VARIJANTI I LIPIDNIH PARAMETARA

MOLEKULARNA I BIOHEMIJSKA KARAKTERIZACIJA FAMILIJARNE HIPERHOLESTEROLEMIJE: POVEZANOST GENETSKIH VARIJANTI I LIPIDNIH PARAMETARA

  • Sandra Singh linic for Endocrinology, Diabetes and Metabolic Disease, Department for Lipid Disorders and Cardiovascular Complications in Diabetes, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Serbia https://orcid.org/0000-0001-6290-0184
  • Vladimir Gašić Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia
  • Jovana Komazec Faculty of Medicine, University of Belgrade, Serbia
  • Ivana Grubiša Faculty of Medicine, University of Belgrade, Serbia
  • Ljiljana Popović Clinic for Endocrinology, Diabetes and Metabolic Disease, Department for Lipid Disorders and Cardiovascular Complications in Diabetes, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Serbia
  • Iva Rasulić Clinic for Endocrinology, Diabetes and Metabolic Disease, Department for Lipid Disorders and Cardiovascular Complications in Diabetes, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Serbia
  • Ana Petakov linic for Endocrinology, Diabetes and Metabolic Disease, Department for Lipid Disorders and Cardiovascular Complications in Diabetes, University Clinical Centre of Serbia, Belgrade
  • Marija Mitrović Clinic for Endocrinology, Diabetes and Metabolic Disease, Department for Lipid Disorders and Cardiovascular Complications in Diabetes, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Serbia
  • Emilija Mihailović Clinic for the Admission and Management of Emergency Internal Medicine Conditions, Emergency Centre, Belgrade, Serbia
  • Sonja Pavlović Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Serbia
  • Katarina Ilić Clinic for Endocrinology, Diabetes and Metabolic Disease, Department for Lipid Disorders and Cardiovascular Complications in Diabetes, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Serbia; Faculty of Medicine, University of Belgrade, Serbia
DOI: https://doi.org/10.5937/jomb0-62224

Abstract


Background: Familial hypercholesterolemia (FH) is characterised by elevated low-density lipoprotein cholesterol (LDL-C) levels and an increased risk of premature cardiovascular disease. The present study aimed to investigate the genetic background and associated biochemical profiles of patients with clinically suspected FH in Serbia. Methods: A total of 101 patients with clinically suspected FH were recruited between 2015 and 2023 from the Clinic for Endocrinology, Diabetes and Metabolic Diseases in Serbia. Clinical diagnosis was established using the Dutch Lipid Clinic Network (DLCN) criteria. Fasting serum lipids (total cholesterol [TC], LDL-C, high-density lipoprotein cholesterol [HDL-C], triglycerides [TG], apolipoprotein A-I [ApoA-I], apolipoprotein B [ApoB], and lipoprotein(a) [Lp(a)]) were measured enzymatically. Genetic testing for LDLR, APOB, PCSK9, and LDLRAP1 genes was performed using next-generation sequencing on the Illumina NextSeq 550DX platform. Variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. Statistical analyses were conducted in SPSS (version 30.0). Results: Pathogenic or likely pathogenic variants were identified in 44 of 101 patients, yielding a mutation detection rate of 43.6%. Genetically confirmed FH patients exhibited significantly higher LDL-C (p<0.001), total cholesterol (p<0.001), triglycerides (p<0.001), and ApoB (p=0.001) compared with mutation-negative individuals, while HDL-C, ApoA-I (p=0.413), and Lp(a) (p=0.421) levels did not differ significantly between groups.

 

Conclusions: This study demonstrates the molecular and biochemical diversity of familial hypercholesterolemia in the Serbian population. Pathogenic FH mutations were associated with higher LDL-C, total cholesterol, and ApoB levels, underscoring the importance of combining genetic testing with lipid profiling for precise diagnosis and management.
Published
2025/11/12
Issue
Ahead of print
Section
Original paper

Copyright (c) 2025 Neda Milinković

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