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. 2025 Jun 14;19(1):66.
doi: 10.1186/s40246-025-00769-y.

Correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patients

Rania A Zahwo #  1 , Ziad N Rezk #  2 , Tamer M Elwasify  3 , Amr M Zaki  4 , Hoda M El Assi  5 , Eman Ramadan  6   7 , Abdallah Y Habib  8 , Wael A Hassan  7 , Ahmed Abdel-Raouf  7 , Ameera Ragheb  7 , Amin F Shaker  7 , Khaled E Amer  7 , Heba Sh Kassem  9
Affiliations

Correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patients

Rania A Zahwo et al. Hum Genomics. .

Abstract

Background: Familial Hypercholesterolemia (FH) is a major risk factor for premature Coronary Artery Disease (CAD). Genetic testing is the gold standard for FH diagnosis. The purpose of this Observational Analytical Cross-sectional study was to estimate the proportion of genetically confirmed Familial Hypercholesterolemia in Patients with premature Coronary Artery Disease in a cohort of Egyptian patients.

Methods: Next generation sequencing (NGS) was conducted for 7 genes (LDLR, PCSK9, APOB, APOE, ABCG5, ABCG8 and LDLRAP1) commonly associated with FH in 94 patients with Premature CAD from 2 tertiary hospitals in Cairo and Alexandria, Egypt. Individuals were clinically assessed using the Dutch Lipid Network criteria and genetically-confirmed FH prevalence was analyzed.

Results: Fourteen patients had pathogenic or likely pathogenic mutations in LDLR, APOB, PCSK9 and LDLRAP1 genes. Three patients had homozygous autosomal dominant FH and another 3 patients had autosomal recessive hypercholesterolemia. In addition, 10 patients had rare variants of uncertain significance in LDLR, APOB, APOE, ABCG5 and ABCG8 genes.

Conclusions: The prevalence of genetically confirmed FH in premature CAD (PCAD) patients in this study was found to be 14.89%. The Dutch Lipid Clinic Network (DLCN) scoring system is suggested as a good screening tool for familial hypercholesterolemia but confirmatory genetic testing is essential for the accurate diagnosis and management of the patients. In Egypt, the high rate of consanguinity contributes to the high prevalence of both homozygous autosomal dominant and recessive FH.

Keywords: DLCN; Egypt; Familial hypercholesterolemia; Genetic testing; IHD; Premature CAD.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the institutional review board of the Armed Forces College of Medicine in Cairo, Egypt (serial number: 128) and Ethics Committee, Faculty of Medicine, Alexandria University (serial number: 0107004). All participants in this study gave a written informed consent. All participants were informed of their right to accept or refuse participation in the study and that they could also withdraw from the study at any time. All procedures conducted were in accordance with institutional guidelines. The study conforms to the principles of the declaration of Helsinki, 2008.(47). Consent for publication: Not applicable. No identifiable patient records were included in this manuscript. Competing interests: The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Genetic testing results across different DLCN classifications of FH
See this image and copyright information in PMC

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