Impact of VKORC1, CYP4F2 and NQO1 gene variants on warfarin dose requirement in Han Chinese patients with catheter ablation for atrial fibrillation

Li, Jiao; Yang, Wenlong; Xie, Zhonghui; Yu, Kun; Chen, Yuhua; Cui, Kaijun

doi:10.1186/s12872-018-0837-x

Cited by 22 publications

(18 citation statements)

References 24 publications

(30 reference statements)

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“…Given this evidence and the once putative role of NQO1 in vitamin K recycling, we and others have examined warfarin dose requirements by the NQO1*2 genotype with mixed results. Although no association has been identified in European or African ancestry populations, 19,40 accumulating data suggest an association in some Latino and Asian populations; although data are not entirely consistent 19,22,41,42 …”

Section: Discussionmentioning

confidence: 99%

“…Although no association has been identified in European or African ancestry populations, 19,40 accumulating data suggest an association in some Latino and Asian populations; although data are not entirely consistent. 19,22,41,42 Latinos who have varying European, African, and Native American ancestral composition share certain haplotypes with Asians, 43 in whom NQO1 associations with warfarin were documented. Our U.S. cohort included Latinos from the UAZ, who are presumably of mostly Mexican descent, as suggested by the genetic ancestry analysis, and UIC, who we previously reported were of predominantly Mexican descent, 19 with mostly European and Native American ancestry.…”

Section: Genetic Warfarin Determinants In Latinosmentioning

confidence: 99%

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Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos

Rouby

Marcatto

Claudio

et al. 2020

Clinical Translational Sci

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We conducted a multi-site investigation of genetic determinants of warfarin dose variability in Latinos from the U.S. and Brazil. Patients from four institutions in the United States (n = 411) and Brazil (n = 663) were genotyped for VKORC1 c.-1639G> A, common CYP2C9 variants, CYP4F2*3, and NQO1*2. Multiple regression analysis was used in the U.S. cohort to test the association between warfarin dose and genotype, adjusting for clinical factors, with further testing in an independent cohort of Brazilians. In the U.S. cohort, VKORC1 and CYP2C9 variants were associated with lower warfarin dose (β = −0.29, P < 2.0 × 10 −16 ; β = −0.21, P = 4.7 × 10 −7 , respectively) whereas CYP4F2 and NQO1 variants were associated with higher dose (β = 0.10, P = 2 × 10 −4 ; β = 0.10, P = 0.01, respectively). Associations with VKORC1 (β = −0.14, P = 2.0 × 10 −16), CYP2C9 (β = −0.07, P = 5.6 × 10 −10), and CYP4F2 (β = 0.03, P = 3 × 10 −3), but not NQO1*2 (β = 0.01, P = 0.30), were replicated in the Brazilians, explaining 43-46% of warfarin dose variability among the cohorts from the U.S. and Brazil, respectively. We identified genetic associations with warfarin dose requirements in the largest cohort of ancestrally diverse, warfarin-treated Latinos from the United States and Brazil to date. We confirmed the association of variants in VKORC1, CYP2C9, and CYP4F2 with warfarin dose in Latinos from the United States and Brazil. Although the use of direct acting oral anticoagulants is increasing, warfarin remains commonly prescribed for prevention and treatment of thromboembolic events. 1,2 Complicating therapy with warfarin is the drug's narrow therapeutic index and high interpatient variability in dose requirements. 3 Latinos are at notably high risk for poor outcomes as a result of nontherapeutic anticoagulation with warfarin. 4-8 Particularly alarming is the increased risk for warfarin-related intracranial hemorrhage in Latinos compared with non-Latino whites. 7 Latinos also have a higher recurrence rate of thrombotic events and worse outcomes from these events compared with whites. 5,

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Section: Discussionmentioning

confidence: 99%

Section: Genetic Warfarin Determinants In Latinosmentioning

confidence: 99%

Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos

Rouby

Marcatto

Claudio

et al. 2020

Clinical Translational Sci

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“…The significance of the functional promoter polymorphism, VKORC1 –1639G>A gene on the warfarin dose requirements has been studied by many researches ( Zhang et al., 2015 ; Topkara et al., 2016 ; Li et al., 2018 ). A meta-analysis including 53 studies showed that most common VKORC1 genotypes in Asian and Caucasian were -1639 AA, -1173 TT and -3730 GG, but the distribution frequency of these three genotypes in Asian was higher than that in Caucasian ( Tang et al., 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Pharmacogenetic-Guided Algorithm to Improve Daily Dose of Warfarin in Elder Han-Chinese Population

et al. 2020

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Objectives: To verify the accuracy of the International Warfarin Pharmacogenetics Consortium (IWPC) algorithm, identify the effects of genetic and clinical factors on warfarin stable dose, and to establish a new warfarin stable dose prediction algorithm for the elderly Han-Chinese population under the guidance of pharmacogenetics. Methods: According to the inclusion criteria, 544 non-valvular atrial fibrillation patients taking warfarin for anticoagulation treatment were enrolled. Data information of three groups including the whole population, people under 65 years old and over 65 years old were substituted into the IWPC algorithm respectively to verify its accuracy. The basic data and clinical information of 360 elderly people were collected for statistical analysis and the genotypes of VKORC1-G1639A and CYP2C9 were detected by Sanger sequencing. The new algorithm of the elder pharmacogenetics warfarin dosing was obtained by stepwise multiple regression. The determination coefficient (R2), root mean squared error (RMSE), and the proportion of the predicted value within the true value range of ±20%(20%-p) were used to evaluate the accuracy of the IWPC algorithm and the new algorithm. Results: Among the three different age groups, the warfarin stable dose predictive accuracy of IWPC algorithm was the lowest in the elderly patients above 65-year-old. In this study, the important factors influencing the stable dose of warfarin in the elderly Han-Chinese were height, weight, body surface area, serum creatinine level, amiodarone usage, CYP2C9 (*1*2, *1*3), and VKORC1 (GG/GA) genotypes. By means of stepwise multiple regression analysis, we established a new elder warfarin dosing algorithm (R 2 =0.3714) containing height, creatinine, amiodarone usage, CYP2C9 (*1*2 or *1*3), and VKORC1 (GA or GG) genotypes. The prediction accuracy and clinical availability of the Elderly algorithm was significantly better than that of IWPC algorithm verified by RMSE, R2, and (20%-p) methods.

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“…A schematic of the literature screening process is shown in Figure 1. A total of 124 articles were screened, and four articles describing 757 patients were included in the meta-analysis [9,25,30,31]. All included studies were published in English between 2007 2Cardiovascular Therapeutics and 2020.…”

Section: Study Identification and Characteristicsmentioning

confidence: 99%

Influence of NQO1 Polymorphisms on Warfarin Maintenance Dose: A Systematic Review and Meta-Analysis (rs1800566 and rs10517)

Tian¹,

Xiao²,

Zhou³

et al. 2021

Cardiovascular Therapeutics

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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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Impact of VKORC1, CYP4F2 and NQO1 gene variants on warfarin dose requirement in Han Chinese patients with catheter ablation for atrial fibrillation

Cited by 22 publications

References 24 publications

Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos

Multi‐site Investigation of Genetic Determinants of Warfarin Dose Variability in Latinos

Pharmacogenetic-Guided Algorithm to Improve Daily Dose of Warfarin in Elder Han-Chinese Population

Influence of NQO1 Polymorphisms on Warfarin Maintenance Dose: A Systematic Review and Meta-Analysis (rs1800566 and rs10517)

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