Clinical relevance of VKORC1 (G‐1639A and C1173T) and CYP2C9*3 among patients on warfarin

@article{Teh2012ClinicalRO,
  title={Clinical relevance of VKORC1 (G‐1639A and C1173T) and CYP2C9*3 among patients on warfarin},
  author={Lay Kek Teh and Immaculate Mbongo Langmia and M. H. Fazleen Haslinda and Harris Abdullah Ngow and M. Roziah and Roslan Harun and Zainul Amiruddin Zakaria and Mohd Zaki Salleh},
  journal={Journal of Clinical Pharmacy and Therapeutics},
  year={2012},
  volume={37}
}
What is known and Objectives:  Testing for cytochrome P450‐2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) variant alleles is recommended by the FDA for dosing of warfarin. However, dose prediction models derived from data obtained in one population may not be applicable to another. We therefore studied the impact of genetic polymorphisms of CYP2C9 and VKORC1 on warfarin dose requirement in Malaysia. 
The impact of VKORC1-1639G > A genetic polymorphism upon warfarin dose requirement in different ethnic populations
TLDR
A meta-analysis indicated that the VKORC1-1639G > A genetic polymorphism is associated with the variation of interindividual warfarin dose requirement in different ethnic populations.
Effect of genetic variants, especially CYP2C9 and VKORC1, on the pharmacology of warfarin.
TLDR
Genetic effects of VKORC1 and CYP2C9 in African and Asian populations are concordant with those in individuals of European ancestry; however, frequency distribution of allelic variants can vary considerably between major populations.
The Contribution of VKORC1 and CYP2C9 Genetic Polymorphisms and Patients’ Demographic Characteristics with Warfarin Maintenance Doses: A Suggested Warfarin Dosing Algorithm
TLDR
This study showed that in the heart valve replacement patients considering VKORC1 and CYP2C9 polymorphisms beside demographic characteristics such as age will be helpful in pre-treatment dosing of warfarin which in turn reduces the complications associated with inappropriate warFarin dosing.
Frequency of Common VKORC1 Polymorphisms and Their Impact on Warfarin Dose Requirement in Pakistani Population
  • A. Qayyum, M. H. Najmi, +5 authors M. Ismail
  • Medicine
    Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
  • 2018
TLDR
There is a need to study genotype frequency distribution and their effect on warfarin dose variability among different populations due to diversity in outcome, and the need for exploration of more genetic and nongenetic factors in Pakistani population is stressed.
Frequency of VKORC1 Gene Polymorphisms and Its Association with Warfarin Dose Requirement in Patients from Mazandaran Province
TLDR
The correlation between dose requirements and INR with polymorphisms was similar to other studies, however, percentage of genotypes in each polymorphism was different from other populations.
Pharmacogenetics of Warfarin in a Diverse Patient Population
Introduction: Many warfarin-related genotypes have shown to impact the average daily warfarin (ADW) dose requirements; however, information in non-Caucasian populations is limited. Objectives: To
Is There a Role for MDR1, EPHX1 and Protein Z Gene Variants in Modulation of Warfarin Dosage? A Study on a Cohort of the Egyptian Population
TLDR
Warfarin dose/week was not influenced by each of the MDR1 C3435T, EPHX1 H139R, and PZ A-13G gene polymorphisms when examined separately, but when these single nucleotide polymorphisms (SNPs) were combined, MDR 1 TT/EPHX1 RH,RR/PZ AA subjects showed statistically significant increase in warfarindose/week.
Differences in CYP2C9 Genotype and Enzyme Activity Between Swedes and Koreans of Relevance for Personalized Medicine: Role of Ethnicity, Genotype, Smoking, Age, and Sex.
TLDR
Ethnicity and environment factors need to be considered together with genotype for population-specific dose optimization and global personalized medicine.
Validation of a Proposed Warfarin Dosing Algorithm Based on the Genetic Make-Up of Egyptian Patients
TLDR
The contribution of genetic and nongenetic factors on the variability of warfarin dose requirements in the Egyptian population is examined using an easy, cost-effective and rapid analysis of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 (CYP) 2C9 single nucleotide polymorphism (SNP) genotyping of patients.
Warfarin Anticoagulant Therapy: A Southern Italy Pharmacogenetics-Based Dosing Model
TLDR
The algorithm, which is based on six polymorphisms, age and gender, is user-friendly and its application in clinical practice could improve the personalized management of patients undergoing warfarin therapy.
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References

SHOWING 1-10 OF 27 REFERENCES
The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements: proposal for a new dosing regimen.
TLDR
The multivariate regression model including the variables of age, CYP2C9 and VKORC1 genotype, and height produced the best model for estimating warfarin dose (R2 = 55%).
Common VKORC1 and GGCX polymorphisms associated with warfarin dose
TLDR
A novel combination of factors that explains almost 60% of variable response to warfarin are reported, andotype-based dose predictions may in future enable personalised drug treatment from the start of warFarin therapy.
Main haplotypes and mutational analysis of vitamin K epoxide reductase (VKORC1) in a Swedish population: a retrospective analysis of case records
TLDR
The result shows that VKORC1*2 is the most important haplotype for warfarin dosage, and patients with VKORP*2 haplotype seem to require much lower warFarin doses than other patients.
Warfarin dose and the pharmacogenomics of CYP2C9 and VKORC1 - rationale and perspectives.
TLDR
Algorithms incorporating genetic (CYP2C9 and VKORC1), demographic, and clinical factors to estimate the warfarin dosage, could potentially minimize the risk of over dose during war Farfarin induction.
Role of pharmacodiagnostic of CYP2C9 variants in the optimization of warfarin therapy in Malaysia: a 6-month follow-up study.
TLDR
Prospective clinical studies are now being conducted to assess dosing algorithms that incorporate the contribution of the genotype to allow the individualization of warfarin dose.
Role of pharmacodiagnostic of CYP2C9 variants in the optimization of warfarin therapy in Malaysia: A 6-month follow-up study
TLDR
The observation clearly highlights the inadequacy of the current dosing regimens and the need to move toward a more individualized approach to warfarin therapy.
Cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) genotypes as determinants of acenocoumarol sensitivity.
TLDR
The simple genotyping of 2 single-nucleotide polymorphisms (SNPs), VKORC1 -1639G>A or 1173C>T and the CYP2C9*3 polymorphisms, could predict a high risk of overdose before initiation of anticoagulation with acenocoumarol, and provide a safer and more individualized antICOagulant therapy.
A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin.
TLDR
Genetic variants of the VKORC1 gene locus modulate the mean daily dose of drug prescribed to acquire the target anticoagulation intensity and accounted for about a third of the interindividual variability in the present setting.
Effect of VKORC1 haplotypes on transcriptional regulation and warfarin dose.
TLDR
VKORC1 haplotypes can be used to stratify patients into low-, intermediate-, and high-dose warfarin groups and may explain differences in dose requirements among patients of different ancestries.
Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2
TLDR
The gene vitamin K epoxide reductase complex subunit 1 (VKORC1), which encodes a small transmembrane protein of the endoplasmic reticulum, is identified, by using linkage information from three species, to be involved in two heritable human diseases.
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