ArticleThe Annals of pharmacotherapy2012
Prediction of warfarin dose reductions in Puerto Rican patients, based on combinatorial CYP2C9 and VKORC1 genotypes.
Article in The Annals of pharmacotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01318057 (Pharmacogenetics of Warfarin in Puerto Rican Patients Using a Physiogenomics Approach.), which is not on this map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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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.
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.
Pharmacogenetics of Warfarin in Puerto Rican Patients Using a Physiogenomics Approach.
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Pharmacogenetic research activity in Central America and the Caribbean: a systematic review.Pharmacogenomics · 2016Pooled it
- Genotype-driven pharmacokinetic simulations of warfarin levels in Puerto Ricans.Drug metabolism and personalized therapy · 2020Article
- CYP2C9*61, a rare missense variant identified in a Puerto Rican patient with low warfarin dose requirements.Pharmacogenomics · 2019Article
- Pharmacogenetics of drug-metabolizing enzymes in US Hispanics.Drug metabolism and personalized therapy · 2015Review
- Pharmacogenetic association study of warfarin safety endpoints in Puerto Ricans.Puerto Rico health sciences journal · 2014Observational
- Does ethnicity play a role in the dosing of warfarin in Hawai'i?Hawai'i journal of medicine & public health : a journal of Asia Pacific Medicine & Public Health · 2014Article
- Association of genetic polymorphisms with warfarin dose requirements in Chinese patients.Genetic testing and molecular biomarkers · 2013Review
- Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients.Pharmacogenomics · 2012Article
- Effect of NQO1 and CYP4F2 genotypes on warfarin dose requirements in Hispanic-Americans and African-Americans.Pharmacogenomics · 2012Article
- Effect of genetic variants, especially CYP2C9 and VKORC1, on the pharmacology of warfarin.Seminars in thrombosis and hemostasis · 2012Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundThe influence of CYP2C9 and VKORC1 polymorphisms on warfarin dose has been investigated in white, Asian, and African American populations but not in Puerto Rican Hispanic patients.
objectiveTo test the associations between genotypes, international normalized ratio (INR) measurements, and warfarin dosing and gauge the impact of these polymorphisms on warfarin dose, using a published algorithm.
methodsA retrospective warfarin pharmacogenetic association study in 106 Puerto Rican patients was performed. DNA samples from patients were assayed for 12 variants in both CYP2C9 and VKORC1 loci by HILOmet PhyzioType assay. Demographic and clinical nongenetic data were retrospectively collected from medical records. Allele and genotype frequencies were determined and Hardy-Weinberg equilibrium (HWE) was tested.
resultsSixty-nine percent of patients were carriers of at least one polymorphism in either the CYP2C9 or the VKORC1 gene. Double, triple, and quadruple carriers accounted for 22%, 5%, and 1%, respectively. No significant departure from HWE was found. Among patients with a given CYP2C9 genotype, warfarin dose requirements declined from GG to AA haplotypes; whereas, within each VKORC1 haplotype, the dose decreased as the number of CYP2C9 variants increased. The presence of these loss-of-function alleles was associated with more out-of-range INR measurements (OR = 1.38) but not with significant INR >4 during the initiation phase. Analyses based on a published pharmacogenetic algorithm predicted dose reductions of up to 4.9 mg/day in carriers and provided better dose prediction in an extreme subgroup of highly sensitive patients, but also suggested the need to improve predictability by developing a customized model for use in Puerto Rican patients.
conclusionsThis study laid important groundwork for supporting a prospective pharmacogenetic trial in Puerto Ricans to detect the benefits of incorporating relevant genomic information into a customized DNA-guided warfarin dosing algorithm.
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