Association between polymorphisms of
            VKORC1
            and
            CYP2C9
            genes with warfarin maintenance dose in a group of warfarin users in Birjand city, Iran

This meta-analysis was conducted to analyze the effect of NQO1 polymorphism on the warfarin maintenance dosage. Using strict inclusion and exclusion criteria, we searched PubMed, EMBASE, and the Cochrane Library for eligible studies published prior to July 7, 2021. The required data were extracted, and experts were consulted when necessary. Review Manager Version 5.4 software was used to analyze the relationship between NQO1 polymorphisms and the warfarin maintenance dosage. Four articles involving 757 patients were included in the meta-analysis. Patients who were NQO1 rs10517 G carriers (AG carriers or GG carriers) required a 48% higher warfarin maintenance dose than those who were AA carriers. Patients with NQO1 rs1800566 CT carriers required a 13% higher warfarin dose than those who were CC carriers, with no associations observed with the other comparisons of the NQO1 rs1800566 genotypes. However, the results obtained by comparing the NQO1 rs1800566 genotypes require confirmation, as significant changes in the results were found in sensitivity analyses. Our meta-analysis suggests that the NQO1 rs10517and NQO1 rs1800566 variant statuses affect the required warfarin maintenance dose.

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The effect of the plasma levels of proteins C and S on the prediction of warfarin maintenance dose requirements

Clinical Pharmacology & Therapeutics ◽

10.1038/clpt.1992.101 ◽

1992 ◽

Vol 52 (1) ◽

pp. 42-49 ◽

Cited By ~ 3

Author(s):

Aharon Lubetsky ◽

Uri Seligsohn ◽

David Ezra ◽

Hillel Halkin

Keyword(s):

Plasma Levels ◽

Maintenance Dose ◽

Warfarin Maintenance Dose

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Influence of Genetic Polymorphisms and Non-Genetic Factors upon Warfarin Maintenance Dose in Japanese Elderly Patients

Rinsho yakuri/Japanese Journal of Clinical Pharmacology and Therapeutics ◽

10.3999/jscpt.42.333 ◽

2011 ◽

Vol 42 (5) ◽

pp. 333-340

Author(s):

Hajime NAKASHIMA ◽

Jun MIURA ◽

Tsukasa UNO ◽

Terufumi MATSUNAGA ◽

Tomonori TATEISHI

Keyword(s):

Elderly Patients ◽

Genetic Polymorphisms ◽

Maintenance Dose ◽

Genetic Factors ◽

Japanese Elderly ◽

Warfarin Maintenance Dose

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Validation of VKORC1 and CYP2C9 genotypes on interindividual warfarin maintenance dose: a prospective study in Chinese patients

Pharmacogenetics and Genomics ◽

10.1097/fpc.0b013e328326e0c7 ◽

2009 ◽

Vol 19 (3) ◽

pp. 226-234 ◽

Cited By ~ 110

Author(s):

Sheng-Wen Huang ◽

Hai-Sheng Chen ◽

Xian-Qun Wang ◽

Ling Huang ◽

Ding-Li Xu ◽

...

Keyword(s):

Prospective Study ◽

Maintenance Dose ◽

Chinese Patients ◽

A Prospective Study ◽

Warfarin Maintenance Dose

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Predicting the warfarin maintenance dose in elderly inpatients at treatment initiation: accuracy of dosing algorithms incorporating or not VKORC1/CYP2C9 genotypes

Journal of Thrombosis and Haemostasis ◽

10.1111/j.1538-7836.2011.04213.x ◽

2011 ◽

Vol 9 (4) ◽

pp. 711-718 ◽

Cited By ~ 20

Author(s):

C. MOREAU ◽

E. PAUTAS ◽

I. GOUIN-THIBAULT ◽

J.-L. GOLMARD ◽

I. MAHÉ ◽

...

Keyword(s):

Maintenance Dose ◽

Treatment Initiation ◽

Elderly Inpatients ◽

Warfarin Maintenance Dose

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Estimation of Warfarin Maintenance Dose Based on VKORC1 (−1639 G>A) and CYP2C9 Genotypes

Clinical Chemistry ◽

10.1373/clinchem.2006.078139 ◽

2007 ◽

Vol 53 (7) ◽

pp. 1199-1205 ◽

Cited By ~ 143

Author(s):

Yusheng Zhu ◽

Michael Shennan ◽

Kristen K Reynolds ◽

Nancy A Johnson ◽

Matthew R Herrnberger ◽

...

Keyword(s):

Body Weight ◽

Maintenance Dose ◽

Plasma Concentrations ◽

Warfarin Dose ◽

Positive Association ◽

Additional Contribution ◽

Allele Specific ◽

Study Population ◽

Warfarin Maintenance Dose ◽

Low Dosage

Abstract Background: CYP2C9 polymorphisms are associated with decreased S-warfarin clearance and lower maintenance dosage. Decreased expression of VKORC1 resulting from the −1639G>A substitution has also been implicated in lower warfarin dose requirements. We investigated the additional contribution of this polymorphism to the variance in warfarin dose. Methods: Sixty-five patients with stable anticoagulation were genotyped for CYP2C9 and VKORC1 with Tag-It™ allele-specific primer extension technology. Plasma S-warfarin concentrations and warfarin maintenance dose were compared among patients on the basis of the VKORC1 −1639G>A genotype. Results: Eighty percent of CYP2C9*1/*1 patients stabilized on <4.0 mg/day warfarin had at least 1 VKORC1 −1639A allele. Mean warfarin doses (SD) were 6.7 (3.3), 4.3 (2.2), and 2.7 (1.2) mg/day for patients with the VKORC1 −1639GG, GA, and AA genotypes, respectively. Steady-state plasma concentrations of S-warfarin were lowest in patients with the VKORC1 −1639AA genotype and demonstrated a positive association with the VKORC1 −1639G allele copy number (trend P = 0.012). A model including VKORC1 and CYP2C9 genotypes, age, sex, and body weight accounted for 61% of the variance in warfarin daily maintenance dose. Conclusions: The VKORC1 −1639A allele accounts for low dosage requirements of most patients without a CYP2C9 variant. Higher plasma S-warfarin concentrations corresponding to increased warfarin maintenance dosages support a hypothesis for increased expression of the VKORC1 −1639G allele. VKORC1 and CYP2C9 genotypes, age, sex, and body weight account for the majority of variance in warfarin dose among our study population.

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