Evidence map›Paper›PMID 36739459›Full record

ArticleThe pharmacogenomics journal2023

Targeted next-generation sequencing of genes involved in Warfarin Pharmacodynamics and pharmacokinetics pathways using the Saudi Warfarin Pharmacogenetic study (SWAP).

Maha Al Ammari, Bader Almuzzaini, Khalid Al Sulaiman, Mohammed AlBalwi, Khizra Sultana, Ibrahim B Alabdulkareem, Nada S Almakhlafi, Anoud Al Humoud, Mohammed Waheeby, Munee Balla and 3 more

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Article in The pharmacogenomics journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 31% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 3 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Maha Al AmmariPharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Bader AlmuzzainiMedical Genomics Research Department, King Abdullah International Medical Research Center, Ministry of National Guard Health Affairs, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.ORCID 0000-0003-1176-9037
Khalid Al SulaimanPharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Mohammed AlBalwiDepartment of Pathology and laboratory, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
Khizra SultanaResearch Office, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia.
Ibrahim B AlabdulkareemHealth Sciences Research Center, King Abdullah Bin Abdulaziz University Hospital, Princess Nourah bint Abdulrahman University, Riyadh, Kingdom of Saudi Arabia.
Nada S AlmakhlafiPharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Anoud Al HumoudPharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Mohammed WaheebyPharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Munee BallaPharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Asma Al ShehriPharmaceutical Care Services, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Adel AlharfSaudi Food and Drug Authority, Drug Sector, Riyadh, Saudi Arabia.
Jahad AlghamdiSaudi Food and Drug Authority, Drug Sector, Riyadh, Saudi Arabia. AlghamdiJahad7@gmail.com.ORCID 0000-0001-7261-8975
King Saud bin Abdulaziz University for Health Sciences · SASaudi Arabian Monetary Authority · SAPrincess Nourah bint Abdulrahman University · SA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundWarfarin is an oral anticoagulant commonly used for treatment and prophylaxis against thromboembolic events. Warfarins's narrow therapeutic index window is one of the main challenges in clinical practice; thus, it requires frequent monitoring and dose adjustment to maintain patients' therapeutic range. Warfarin dose variation and response are attributed to several inter-and intra-individuals factors, including genetic variants in enzymes involved in warfarin pharmacokinetics (PK) and pharmacodynamics (PD) pathways. Thus, we aim to utilize the next-generation sequencing (NGS) approach to identify rare and common genetic variants that might be associated with warfarin responsiveness. METHOD AND

resultsA predesigned NGS panel that included 16 genes involved in Warfarin PK/PD pathways was used to sequence 786 patients from the Saudi Warfarin Pharmacogenetic Cohort (SWAP). Identified variants were annotated using several annotation tools to identify the pathogenicity and allele frequencies of these variants. We conducted variants-level association tests with warfarin dose. We identified 710 variants within the sequenced genes; 19% were novel variants, with the vast majority being scarce variants. The genetic association tests showed that VKORC1 (rs9923231, and rs61742245), CYP2C9 (rs98332238, rs9332172, rs1057910, rs9332230, rs1799853, rs1057911, and rs9332119), CYP2C19 (rs28399511, and rs3758581), and CYP2C8 (rs11572080 and rs10509681) were significantly associated with warfarin weekly dose. Our model included genetics, and non-genetic factors explained 40.1% of warfarin dose variation.

conclusionThe study identifies novel variants associated with warfarin dose in the Saudi population. These variants are more likely to be population-specific variants, suggesting that population-specific studies should be conducted before adopting a universal warfarin genotype-guided dosing algorithm.

Indexed as

Pharmacogenomic TestingWarfarinAnticoagulantsCytochrome P-450 CYP2C9Dose-Response Relationship, DrugGenotypeHigh-Throughput Nucleotide SequencingHumansSaudi ArabiaVitamin K Epoxide ReductasesAnticoagulantsCytochrome P-450 CYP2C9Vitamin K Epoxide ReductasesVKORC1 protein, humanWarfarin

Identifiers

PMID36739459
OpenAlexW4319262287

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.