Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population

<h3>Purpose</h3><p dir="ltr">To identify the impact of <i>CYP2C9*2, *3, VKORC1−1639 G>A </i>and <i>CYP4F2*3</i> on warfarin dose in an Arab population. To compare the accuracy of a clinical warfarin dosing (CWD) versus genetic warfarin dosing al...

Full description

Saved in:
Bibliographic Details
Main Author: Amr M. Fahmi (21632909) (author)
Other Authors: Ahmed El Bardissy (22155949) (author), Mohamed Omar Saad (12535545) (author), Amr Fares (22155952) (author), Ahmed Sadek (4588474) (author), Mohamed Nabil Elshafei (9960500) (author), Asma Eltahir (14158923) (author), Asmaa Mohamed (19870274) (author), Hazem Elewa (3592601) (author)
Published: 2024
Subjects:
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1864513540434427904
author Amr M. Fahmi (21632909)
author2 Ahmed El Bardissy (22155949)
Mohamed Omar Saad (12535545)
Amr Fares (22155952)
Ahmed Sadek (4588474)
Mohamed Nabil Elshafei (9960500)
Asma Eltahir (14158923)
Asmaa Mohamed (19870274)
Hazem Elewa (3592601)
author2_role author
author
author
author
author
author
author
author
author_facet Amr M. Fahmi (21632909)
Ahmed El Bardissy (22155949)
Mohamed Omar Saad (12535545)
Amr Fares (22155952)
Ahmed Sadek (4588474)
Mohamed Nabil Elshafei (9960500)
Asma Eltahir (14158923)
Asmaa Mohamed (19870274)
Hazem Elewa (3592601)
author_role author
dc.creator.none.fl_str_mv Amr M. Fahmi (21632909)
Ahmed El Bardissy (22155949)
Mohamed Omar Saad (12535545)
Amr Fares (22155952)
Ahmed Sadek (4588474)
Mohamed Nabil Elshafei (9960500)
Asma Eltahir (14158923)
Asmaa Mohamed (19870274)
Hazem Elewa (3592601)
dc.date.none.fl_str_mv 2024-09-25T15:00:00Z
dc.identifier.none.fl_str_mv 10.1016/j.cpcardiol.2024.102865
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Accuracy_of_an_internationally_validated_genetic-guided_warfarin_dosing_algorithm_compared_to_a_clinical_algorithm_in_an_Arab_population/30024427
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
Biomedical and clinical sciences
Pharmacology and pharmaceutical sciences
Warfarin/administration and dosage
Clinical warfarin dosing
Genetic guided warfarin dosing
VKORC1
CYP2C9
CYP4F2
dc.title.none.fl_str_mv Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <h3>Purpose</h3><p dir="ltr">To identify the impact of <i>CYP2C9*2, *3, VKORC1−1639 G>A </i>and <i>CYP4F2*3</i> on warfarin dose in an Arab population. To compare the accuracy of a clinical warfarin dosing (CWD) versus genetic warfarin dosing algorithms (GWD) during warfarin initiation. </p><h3>Methods</h3><p dir="ltr">A cohort of Arab patients newly starting on warfarin had their dose calculated using CWD published in www.warfarindosing.org and were followed for 1 month. Each patient provided a saliva sample. DNA was extracted, purified and genotyped for <i>VKORC−1639 G>A, CYP2C9*2, CYP2C9*3 </i>and<i> CYP4F2*3</i>. After reaching warfarin maintenance dose, the dose was recalculated using the GWD and median absolute error (MAE) and the percentage of warfarin doses within 20% of the actual dose were calculated and compared for the two algorithms. </p><h3>Results</h3><p dir="ltr">The study enrolled 130 patients from 12 Arabian countries. Compared to those with wild type, carriers of reduced function alleles in <i>CYP2C9</i> required significantly lower median (IQR) warfarin weekly dose [24.5 (15.3) vs. 35 (29.8) mg/week, p=0.006]. With regards to VKORC, patients with AA genotype had a significantly lower median (IQR) weekly warfarin dose compared to AG and GG [21(10.5) vs 29.4 (21), p<0.001 for AA vs AG, p<0.001 for AA vs GG]. The MAE (IQR) for the weekly dose of the GWD was significantly lower compared to CWD [8.1 (10.5) vs 12.4 (12.6) (p<0.001)]. </p><h3>Conclusion</h3><p dir="ltr"><i>CYP2C9 </i>and<i> VKORC1</i> variants are important determinants of warfarin dose in the Arab population. The use of the genetic and clinical factors led to better warfarin dose estimation when compared to clinical factors alone.</p><h2>Other Information</h2><p dir="ltr">Published in: Current Problems in Cardiology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.cpcardiol.2024.102865" target="_blank">https://dx.doi.org/10.1016/j.cpcardiol.2024.102865</a></p>
eu_rights_str_mv openAccess
id Manara2_a85a1de1f33717d1db12d31c3151d1a7
identifier_str_mv 10.1016/j.cpcardiol.2024.102865
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/30024427
publishDate 2024
repository.mail.fl_str_mv
repository.name.fl_str_mv
repository_id_str
rights_invalid_str_mv CC BY 4.0
spelling Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab populationAmr M. Fahmi (21632909)Ahmed El Bardissy (22155949)Mohamed Omar Saad (12535545)Amr Fares (22155952)Ahmed Sadek (4588474)Mohamed Nabil Elshafei (9960500)Asma Eltahir (14158923)Asmaa Mohamed (19870274)Hazem Elewa (3592601)Biological sciencesGeneticsBiomedical and clinical sciencesPharmacology and pharmaceutical sciencesWarfarin/administration and dosageClinical warfarin dosingGenetic guided warfarin dosingVKORC1CYP2C9CYP4F2<h3>Purpose</h3><p dir="ltr">To identify the impact of <i>CYP2C9*2, *3, VKORC1−1639 G>A </i>and <i>CYP4F2*3</i> on warfarin dose in an Arab population. To compare the accuracy of a clinical warfarin dosing (CWD) versus genetic warfarin dosing algorithms (GWD) during warfarin initiation. </p><h3>Methods</h3><p dir="ltr">A cohort of Arab patients newly starting on warfarin had their dose calculated using CWD published in www.warfarindosing.org and were followed for 1 month. Each patient provided a saliva sample. DNA was extracted, purified and genotyped for <i>VKORC−1639 G>A, CYP2C9*2, CYP2C9*3 </i>and<i> CYP4F2*3</i>. After reaching warfarin maintenance dose, the dose was recalculated using the GWD and median absolute error (MAE) and the percentage of warfarin doses within 20% of the actual dose were calculated and compared for the two algorithms. </p><h3>Results</h3><p dir="ltr">The study enrolled 130 patients from 12 Arabian countries. Compared to those with wild type, carriers of reduced function alleles in <i>CYP2C9</i> required significantly lower median (IQR) warfarin weekly dose [24.5 (15.3) vs. 35 (29.8) mg/week, p=0.006]. With regards to VKORC, patients with AA genotype had a significantly lower median (IQR) weekly warfarin dose compared to AG and GG [21(10.5) vs 29.4 (21), p<0.001 for AA vs AG, p<0.001 for AA vs GG]. The MAE (IQR) for the weekly dose of the GWD was significantly lower compared to CWD [8.1 (10.5) vs 12.4 (12.6) (p<0.001)]. </p><h3>Conclusion</h3><p dir="ltr"><i>CYP2C9 </i>and<i> VKORC1</i> variants are important determinants of warfarin dose in the Arab population. The use of the genetic and clinical factors led to better warfarin dose estimation when compared to clinical factors alone.</p><h2>Other Information</h2><p dir="ltr">Published in: Current Problems in Cardiology<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1016/j.cpcardiol.2024.102865" target="_blank">https://dx.doi.org/10.1016/j.cpcardiol.2024.102865</a></p>2024-09-25T15:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1016/j.cpcardiol.2024.102865https://figshare.com/articles/journal_contribution/Accuracy_of_an_internationally_validated_genetic-guided_warfarin_dosing_algorithm_compared_to_a_clinical_algorithm_in_an_Arab_population/30024427CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/300244272024-09-25T15:00:00Z
spellingShingle Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population
Amr M. Fahmi (21632909)
Biological sciences
Genetics
Biomedical and clinical sciences
Pharmacology and pharmaceutical sciences
Warfarin/administration and dosage
Clinical warfarin dosing
Genetic guided warfarin dosing
VKORC1
CYP2C9
CYP4F2
status_str publishedVersion
title Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population
title_full Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population
title_fullStr Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population
title_full_unstemmed Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population
title_short Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population
title_sort Accuracy of an internationally validated genetic-guided warfarin dosing algorithm compared to a clinical algorithm in an Arab population
topic Biological sciences
Genetics
Biomedical and clinical sciences
Pharmacology and pharmaceutical sciences
Warfarin/administration and dosage
Clinical warfarin dosing
Genetic guided warfarin dosing
VKORC1
CYP2C9
CYP4F2