Correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patients
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...
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2025-06-01
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| Series: | Human Genomics |
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| Online Access: | https://doi.org/10.1186/s40246-025-00769-y |
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| author | Rania A. Zahwo Ziad N. Rezk Tamer M. Elwasify Amr M. Zaki Hoda M. El Assi Eman Ramadan Abdallah Y. Habib Wael A. Hassan Ahmed Abdel-Raouf Ameera Ragheb Amin F. Shaker Khaled E. Amer Heba Sh. Kassem |
| author_facet | Rania A. Zahwo Ziad N. Rezk Tamer M. Elwasify Amr M. Zaki Hoda M. El Assi Eman Ramadan Abdallah Y. Habib Wael A. Hassan Ahmed Abdel-Raouf Ameera Ragheb Amin F. Shaker Khaled E. Amer Heba Sh. Kassem |
| author_sort | Rania A. Zahwo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6e37cb7174cf4f5cb5251e2a46daba50 |
| institution | Kabale University |
| issn | 1479-7364 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Human Genomics |
| spelling | doaj-art-6e37cb7174cf4f5cb5251e2a46daba502025-08-20T03:45:32ZengBMCHuman Genomics1479-73642025-06-0119111410.1186/s40246-025-00769-yCorrelation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patientsRania A. Zahwo0Ziad N. Rezk1Tamer M. Elwasify2Amr M. Zaki3Hoda M. El Assi4Eman Ramadan5Abdallah Y. Habib6Wael A. Hassan7Ahmed Abdel-Raouf8Ameera Ragheb9Amin F. Shaker10Khaled E. Amer11Heba Sh. Kassem12Clinical Genomics Center, Faculty of Medicine, Alexandria UniversityMedical Genetics Department, Armed Forces College of MedicineCardiology Department, Armed Forces College of MedicineCardiology Department, Faculty of Medicine, Alexandria UniversityClinical Genomics Center, Faculty of Medicine, Alexandria UniversityPharmacology and Toxicology Department, Faculty of Pharmacy, The British University in EgyptClinical Pathology Department, Military Medical AcademyEgypt Center for Research and Regenerative MedicineEgypt Center for Research and Regenerative MedicineEgypt Center for Research and Regenerative MedicineEgypt Center for Research and Regenerative MedicineEgypt Center for Research and Regenerative MedicineClinical Genomics Center, Faculty of Medicine, Alexandria UniversityAbstract 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.https://doi.org/10.1186/s40246-025-00769-yDLCNFamilial hypercholesterolemiaGenetic testingPremature CADIHDEgypt |
| spellingShingle | Rania A. Zahwo Ziad N. Rezk Tamer M. Elwasify Amr M. Zaki Hoda M. El Assi Eman Ramadan Abdallah Y. Habib Wael A. Hassan Ahmed Abdel-Raouf Ameera Ragheb Amin F. Shaker Khaled E. Amer Heba Sh. Kassem Correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patients Human Genomics DLCN Familial hypercholesterolemia Genetic testing Premature CAD IHD Egypt |
| title | Correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patients |
| title_full | Correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patients |
| title_fullStr | Correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patients |
| title_full_unstemmed | Correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patients |
| title_short | Correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of Egyptian patients |
| title_sort | correlation between clinical classification and genetic analysis of familial hypercholesterolemia in premature coronary artery disease in a cohort of egyptian patients |
| topic | DLCN Familial hypercholesterolemia Genetic testing Premature CAD IHD Egypt |
| url | https://doi.org/10.1186/s40246-025-00769-y |
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