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The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects

Familial hypercholesterolemia (FH) is an inherited disease characterized by reduced efficiency of low-density lipoprotein-cholesterol (LDL-C) removal from the blood and, consequently, an increased risk of life-threatening early cardiovascular complications. In Qatar, the prevalence of FH has not bee...

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Autores principales: Diboun, Ilhame, Al-Sarraj, Yasser, Toor, Salman M., Mohammed, Shaban, Qureshi, Nadeem, Al Hail, Moza S. H., Jayyousi, Amin, Al Suwaidi, Jassim, Albagha, Omar M. E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337875/
https://www.ncbi.nlm.nih.gov/pubmed/35910211
http://dx.doi.org/10.3389/fgene.2022.927504
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author Diboun, Ilhame
Al-Sarraj, Yasser
Toor, Salman M.
Mohammed, Shaban
Qureshi, Nadeem
Al Hail, Moza S. H.
Jayyousi, Amin
Al Suwaidi, Jassim
Albagha, Omar M. E.
author_facet Diboun, Ilhame
Al-Sarraj, Yasser
Toor, Salman M.
Mohammed, Shaban
Qureshi, Nadeem
Al Hail, Moza S. H.
Jayyousi, Amin
Al Suwaidi, Jassim
Albagha, Omar M. E.
author_sort Diboun, Ilhame
collection PubMed
description Familial hypercholesterolemia (FH) is an inherited disease characterized by reduced efficiency of low-density lipoprotein-cholesterol (LDL-C) removal from the blood and, consequently, an increased risk of life-threatening early cardiovascular complications. In Qatar, the prevalence of FH has not been determined and the disease, as in many countries, is largely underdiagnosed. In this study, we combined whole-genome sequencing data from the Qatar Genome Program with deep phenotype data from Qatar Biobank for 14,056 subjects to determine the genetic spectrum and estimate the prevalence of FH in Qatar. We used the Dutch Lipid Clinic Network (DLCN) as a diagnostic tool and scrutinized 11 FH-related genes for known pathogenic and possibly pathogenic mutations. Results revealed an estimated prevalence of 0.8% (1:125) for definite/probable cases of FH in the Qatari population. We detected 16 known pathogenic/likely pathogenic mutations in LDLR and one in PCSK9; all in a heterozygous state with high penetrance. The most common mutation was rs1064793799 (c.313+3A >C) followed by rs771019366 (p.Asp90Gly); both in LDLR. In addition, we identified 18 highly penetrant possibly pathogenic variants, of which 5 were Qatari-specific, in LDLR, APOB, PCSK9 and APOE, which are predicted to be among the top 1% most deleterious mutations in the human genome but further validations are required to confirm their pathogenicity. We did not detect any homozygous FH or autosomal recessive mutations in our study cohort. This pioneering study provides a reliable estimate of FH prevalence in Qatar based on a significantly large population-based cohort, whilst uncovering the spectrum of genetic variants associated with FH.
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spelling pubmed-93378752022-07-30 The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects Diboun, Ilhame Al-Sarraj, Yasser Toor, Salman M. Mohammed, Shaban Qureshi, Nadeem Al Hail, Moza S. H. Jayyousi, Amin Al Suwaidi, Jassim Albagha, Omar M. E. Front Genet Genetics Familial hypercholesterolemia (FH) is an inherited disease characterized by reduced efficiency of low-density lipoprotein-cholesterol (LDL-C) removal from the blood and, consequently, an increased risk of life-threatening early cardiovascular complications. In Qatar, the prevalence of FH has not been determined and the disease, as in many countries, is largely underdiagnosed. In this study, we combined whole-genome sequencing data from the Qatar Genome Program with deep phenotype data from Qatar Biobank for 14,056 subjects to determine the genetic spectrum and estimate the prevalence of FH in Qatar. We used the Dutch Lipid Clinic Network (DLCN) as a diagnostic tool and scrutinized 11 FH-related genes for known pathogenic and possibly pathogenic mutations. Results revealed an estimated prevalence of 0.8% (1:125) for definite/probable cases of FH in the Qatari population. We detected 16 known pathogenic/likely pathogenic mutations in LDLR and one in PCSK9; all in a heterozygous state with high penetrance. The most common mutation was rs1064793799 (c.313+3A >C) followed by rs771019366 (p.Asp90Gly); both in LDLR. In addition, we identified 18 highly penetrant possibly pathogenic variants, of which 5 were Qatari-specific, in LDLR, APOB, PCSK9 and APOE, which are predicted to be among the top 1% most deleterious mutations in the human genome but further validations are required to confirm their pathogenicity. We did not detect any homozygous FH or autosomal recessive mutations in our study cohort. This pioneering study provides a reliable estimate of FH prevalence in Qatar based on a significantly large population-based cohort, whilst uncovering the spectrum of genetic variants associated with FH. Frontiers Media S.A. 2022-07-15 /pmc/articles/PMC9337875/ /pubmed/35910211 http://dx.doi.org/10.3389/fgene.2022.927504 Text en Copyright © 2022 Diboun, Al-Sarraj, Toor, Mohammed, Qureshi, Al Hail, Jayyousi, Al Suwaidi and Albagha. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Diboun, Ilhame
Al-Sarraj, Yasser
Toor, Salman M.
Mohammed, Shaban
Qureshi, Nadeem
Al Hail, Moza S. H.
Jayyousi, Amin
Al Suwaidi, Jassim
Albagha, Omar M. E.
The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects
title The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects
title_full The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects
title_fullStr The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects
title_full_unstemmed The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects
title_short The Prevalence and Genetic Spectrum of Familial Hypercholesterolemia in Qatar Based on Whole Genome Sequencing of 14,000 Subjects
title_sort prevalence and genetic spectrum of familial hypercholesterolemia in qatar based on whole genome sequencing of 14,000 subjects
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337875/
https://www.ncbi.nlm.nih.gov/pubmed/35910211
http://dx.doi.org/10.3389/fgene.2022.927504
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