Observational studyThe pharmacogenomics journal2020
The effect of genetic and nongenetic factors on warfarin dose variability in Qatari population.
Observational study in The pharmacogenomics journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genomewide association analysis of warfarin dose requirements in Middle Eastern and North African populations.Clinical and translational science · 2022Pooled it
- QPGx-CARES: Qatar pharmacogenetics clinical applications and research enhancement strategies.Clinical and translational science · 2024Review
- The investigation of connection between anticoagulant therapy and vitamin K homologues in human determined by LC-MS/MS.Bioanalysis · 2024Article
- Targeted next-generation sequencing of genes involved in Warfarin Pharmacodynamics and pharmacokinetics pathways using the Saudi Warfarin Pharmacogenetic study (SWAP).The pharmacogenomics journal · 2023Article
- Developing Chinese race-specific warfarin dose prediction algorithms.International journal of clinical pharmacy · 2023Article
- Ancestry-related distribution of Runs of homozygosity and functional variants in Qatari population.BMC genomic data · 2022Article
- A population study of clinically actionable genetic variation affecting drug response from the Middle East.NPJ genomic medicine · 2022Article
- Drive-up INR testing and phone-based consultations service during COVID-19 pandemic in a pharmacist-lead anticoagulation clinic in Qatar: Monitoring, clinical, resource utilization, and patient- oriented outcomes.Journal of the American College of Clinical Pharmacy : JACCP · 2021Article
- Anticoagulation clinic drive-up service during COVID-19 pandemic in Qatar.Journal of thrombosis and thrombolysis · 2021Article
- Genetic and Non-Genetic Factors Impact on INR Normalization in Preprocedural Warfarin Management.Pharmacogenomics and personalized medicine · 2021Article
- Effect of SAMe-TTJournal of thrombosis and thrombolysis · 2020Observational
- Derivation and Validation of a Genotype- Guided Warfarin Dosing Model in a Mixed Arab Population.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisArticle
Corrections and comments
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The objective of this study is to estimate the prevalence of VKORC1, CYP2C9, and CYP4F2 genetic variants and their contribution to warfarin dose variability in Qataris. One hundred and fifty warfarin-treated Qatari patients on a stable dose and with a therapeutic INR for at least three consecutive clinic visits were recruited. Saliva samples were collected using Oragene DNA self-collection kit, followed by DNA purification and genotyping via TaqMan Real-Time-PCR assay. The population was stratified into derivation and validation cohorts for the dosing model. The minor allele frequency (MAF) of VKORC1 (-1639G>A) was A (0.47), while the MAF's for the CYP2C9*2 and *3 and CYP4F2*3 were T (0.12), C (0.04) and T (0.43), respectively. Carriers of at least one CYP2C9 decreased function allele (*2 or *3) required lower median (IQR) warfarin doses compared to noncarriers [24.5 (14.5) mg/week vs. 35 (21) mg/week, p < 0.001]. Similarly, carriers of each additional copy of (A) variant in VKORC1 (-1639G>A) led to reduction in warfarin dose requirement compared to noncarriers [21(7.5) vs. 31.5(18.7) vs. 43.7(15), p < 0.0001]. CYP4F2*3 polymorphism on the other hand was not associated with warfarin dose. Multivariate analysis on the derivation cohort (n = 104) showed that a dosing model consisting of hypertension (HTN), heart failure (HF), VKORC1 (-1639G>A), CYP2C9*2 & *3, and smoking could explain 39.2% of warfarin dose variability in Qataris (P < 0.001). In the validation cohort (n = 45), correlation between predicted and actual warfarin doses was moderate (Spearman's rho correlation coefficient = 0.711, p < 0.001). This study concluded that VKORC1 (-1639G>A), CYP2C9*2 & *3 are the most significant predictors of warfarin dose along with HTN, HF and smoking.
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