Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1784759851428085760 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9337875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT dibounilhame theprevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT alsarrajyasser theprevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT toorsalmanm theprevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT mohammedshaban theprevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT qureshinadeem theprevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT alhailmozash theprevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT jayyousiamin theprevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT alsuwaidijassim theprevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT albaghaomarme theprevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT dibounilhame prevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT alsarrajyasser prevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT toorsalmanm prevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT mohammedshaban prevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT qureshinadeem prevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT alhailmozash prevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT jayyousiamin prevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT alsuwaidijassim prevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects AT albaghaomarme prevalenceandgeneticspectrumoffamilialhypercholesterolemiainqatarbasedonwholegenomesequencingof14000subjects |