ArticleMolecular diagnosis & therapy2014
Polymorphisms of CYP2C9, VKORC1, MDR1, APOE and UGT1A1 genes and the therapeutic warfarin dose in Brazilian patients with thrombosis: a prospective cohort study.
Article in Molecular diagnosis & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 27 citations in OpenAlex.
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- Cardiovascular Pharmacogenomics: An Update on Clinical Studies of Antithrombotic Drugs in Brazilian Patients.Molecular diagnosis & therapy · 2021Review
- Non-genetic factors and polymorphisms in genes CYP2C9 and VKORC1: predictive algorithms for TTR in Brazilian patients on warfarin.European journal of clinical pharmacology · 2020Article
- Algorithm for predicting low maintenance doses of warfarin using age and polymorphisms in genes CYP2C9 and VKORC1 in Brazilian subjects.The pharmacogenomics journal · 2020Article
- Polymorphisms ofThe application of clinical genetics · 2019Article
- Association BetweenFrontiers in pharmacology · 2018Article
- The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients.European journal of clinical pharmacology · 2017Article
- Correlation between Rs2108622 Locus of CYP4F2 Gene Single Nucleotide Polymorphism and Warfarin Dosage in Iranian Cardiovascular Patients.Iranian journal of pharmaceutical research : IJPR · 2017Article
- Association of Warfarin Therapy withIranian journal of pharmaceutical research : IJPR · 2017Article
- Association of apolipoprotein E (APOE) polymorphisms with warfarin maintenance dose in a northern Han Chinese population.Lipids in health and disease · 2016Article
- A multi-factorial analysis of response to warfarin in a UK prospective cohort.Genome medicine · 2016Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThere are several pharmacogenetic algorithms to determine the warfarin doses required in patients treated for thromboembolism, but they only explain 60% of dose variation, suggesting that other genes may influence the dose required.
objectivesThis study aimed to evaluate the impact of clinical factors and CYP2C9*2, CYP2C9*3, VKORC1-1639G>A, MDR1 3435C>T, APOE* ε4, and UGT1A1(TA)n polymorphisms on the warfarin dose required, especially in those individuals requiring a high warfarin dose.
methodsWe studied 116 Brazilian patients who received warfarin therapy for thromboembolism. Associations between dose variability and age, body mass index (BMI), gender, use of warfarin antagonists, and genetic polymorphisms were examined.
resultsCYP2C9*2, CYP2C9*3, VKORC1-1639G>A, and APOE *ε4 were associated with lower warfarin doses. Of these subjects, 21% required a warfarin dose higher than 70 mg/week, which was associated with a BMI greater than 25 kg/m(2), use of warfarin antagonists, and the presence of the MDR1 3435T allele and UGT1A1(TA) 7 polymorphism. These individuals were considered to exhibit warfarin resistance. The individuals with the MDR1 3435TT genotype required a dose 21% higher than that required by 3435CT and 3435CC individuals. The UGT1A1(TA) 7 allele was positively correlated with the warfarin dose.
conclusionCYP2C9*2, CYP2C9*3, VKORC1-1639G>A, and APOE *ε4 were associated with lower warfarin doses, while MDR1 3435C>T and UGT1A1(TA) n polymorphisms were associated with a requirement for higher doses. This is the first study to evaluate warfarin resistance, APOE *ε4 and UGT1A1(TA) n genotypes in the Brazilian population, and the association of these two genotypes with warfarin dose required.
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