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 Klinika za endokrinologiju, dijabetes i metaboličke bolesti, Odeljenje za poremećaje lipida i kardiovaskularne komplikacije kod dijabetesa, Univerzitetski klinički centar Srbije, Beograd; Medicinski fakultet, Univerzitet u Beogradu, Srbija https://orcid.org/0000-0001-6290-0184
  • Vladimir Gašić Institut za molekularnu genetiku i genetski inžinjering, Univerzitet u Beogradu, Srbija
  • Jovana Komazec Medicinski fakultet, Univerzitet u Beogradu, Srbija
  • Ivana Grubiša Medicinski fakultet, Univerzitet u Beogradu, Beograd, Srbija
  • Ljiljana Popović Klinika za endokrinologiju, dijabetes i metaboličke bolesti, Odeljenje za poremećaje lipida i kardiovaskularne komplikacije kod dijabetesa, Univerzitetski klinički centar Srbije, Beograd; Medicinski fakultet, Univerzitet u Beogradu, Srbija; Medicinski fakultet, Univerzitet u Beogradu, Srbija
  • Iva Rasulić Klinika za endokrinologiju, dijabetes i metaboličke bolesti, Odeljenje za poremećaje lipida i kardiovaskularne komplikacije kod dijabetesa, Univerzitetski klinički centar Srbije, Beograd; Medicinski fakultet, Univerzitet u Beogradu, Srbija; Medicinski fakultet, Univerzitet u Beogradu, Srbija
  • Ana Petakov Klinika za endokrinologiju, dijabetes i metaboličke bolesti, Odeljenje za poremećaje lipida i kardiovaskularne komplikacije kod dijabetesa, Univerzitetski klinički centar Srbije, Beograd
  • Marija Mitrović Klinika za endokrinologiju, dijabetes i metaboličke bolesti, Odeljenje za poremećaje lipida i kardiovaskularne komplikacije kod dijabetesa, Univerzitetski klinički centar Srbije, Beograd; Medicinski fakultet, Univerzitet u Beogradu, Srbija; Medicinski fakultet, Univerzitet u Beogradu, Srbija
  • Emilija Mihailović Klinika za prijem i lečenje hitnih internističkih stanja, Urgentni centar, Beograd, Srbija
  • Sonja Pavlović Institut za molekularnu genetiku i genetski inžinjering, Univerzitet u Beogradu, Srbija
  • Katarina Ilić Klinika za endokrinologiju, dijabetes i metaboličke bolesti, Odeljenje za poremećaje lipida i kardiovaskularne komplikacije kod dijabetesa, Univerzitetski klinički centar Srbije, Beograd; Medicinski fakultet, Univerzitet u Beogradu, Srbija; Medicinski fakultet, Univerzitet u Beogradu, Srbija; Medicinski fakultet, Univerzitet u Beogradu, Srbija
DOI: https://doi.org/10.5937/jomb0-62224

Sažetak


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.
Objavljeno
2025/11/12
Broj časopisa
Ahead of print
Rubrika
Original paper

Sva prava zadržana (c) 2025 Neda Milinković

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