Influence of CYP4F2 genotype on warfarin dose requirement–a systematic review and meta-analysis

Liang, Ruofei; Zhao, Hong; Huang, Jie; Hu, Dayi; Sun, Yaxun

doi:10.1016/j.thromres.2011.11.043

Cited by 56 publications

(47 citation statements)

References 36 publications

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“…To the best of our knowledge, this is the first study to explore the association between CYP4F2 and the warfarin stable dose solely for the Asian population. As opposed to the studies by Danese et al (16) and Liang et al (17), a statistical difference was observed between the CT and TT genotype, which may be an indication of a larger effect of CYP4F2 on the warfarin dose in the Asian population.…”

Section: Discussioncontrasting

confidence: 96%

“…However, the findings are inconsistent, particularly for Asian patients (10)(11)(12)(13)(14)(15). In 2012, two results of meta-analyses showed that the CYP4F2 gene polymorphism was associated with the CYP4F2 gene polymorphisms on the warfarin maintenance dose: A systematic review and meta-analysis XUE SUN 1,2 , WAN-YING YU 1,2 , WAN-LE MA 1 , LI-HUA HUANG 3 and GUO-PING YANG warfarin maintenance dosage (16,17). However, as they all focused on the studies of European and American populations, the impact of the CYP4F2 genotype on warfarin dose in the Asian population has not been investigated adequately.…”

Section: Introductionmentioning

confidence: 99%

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Impact of the CYP4F2 gene polymorphisms on the warfarin maintenance dose: A systematic review and meta-analysis

Sun

et al. 2016

Biomedical Reports

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Abstract.Warfarin is an oral anticoagulant with significant interpatient variability in dosage. A large number of studies have confirmed that the individual warfarin dose is mainly affected by the cytochrome P450 complex subunit 2C9 and vitamin K epoxide reductase complex subunit 1. However, the association between cytochrome P450 4F2 (CYP4F2) gene polymorphisms and warfarin dosage in the Asian population remains controversial. To investigate the impact of the CYP4F2 polymorphism rs2108622 (p.V433M) on warfarin dose requirement, a systematic review and meta-analysis were conducted. According to the strict inclusion and exclusion criteria set, a comprehensive literature search was performed, and the studies published before August 5, 2015 were searched for in PubMed, EMBASE and the China National Knowledge Infrastructure databases. The references were checked by two independent reviewers. The association between the warfarin maintenance dose and CYP4F2 polymorphism was analyzed. Twenty-two studies were included in the meta-analysis. Compared with the CYP4F2 genotype CC, carriers of the CT and TT genotypes required a 9 [95% confidence interval (CI): 6.0-13.0] and 20% (95% CI, 13.0-27.0) higher warfarin dose, respectively. In the combined analysis, T carriers (CT+TT) required an 11% (95% CI, 8.0-14.0) higher warfarin dose compared to the CC genotype. In addition, there was a 10% (95% CI, 5.0-15.0) higher warfarin dose in TT carriers compared to the CT genotype (all P<0.05). The results of the meta-analysis suggest that the effects of the CYP4F2 polymorphism on individual warfarin dose have a statistically significant difference, and the effect degree is variable in the subgroups. Further studies are expected to explore whether the pharmacogenetics model including the CYP4F2 polymorphism can strengthen the prediction of warfarin dose. IntroductionWarfarin is a commonly oral anticoagulant, mainly used clinically in the treatment of thromboembolic diseases, such as atrial fibrillation (AF) and deep venous thrombosis (DVT); however, the existence of high interpatient variability in drug dosage may increase the risk of bleeding or thrombosis. Studies indicated that individual warfarin dose was influenced by a host of factors, including genetic and environmental factors. Genetic factors are one of the main reasons for the individual difference in warfarin maintenance dosage. Previous studies have also suggested that cytochrome P450 complex subunit 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphisms, age, weight and body surface area can explain ~50% of the influence on warfarin dose requirement (1-6). Therefore, there remains a 50% uncertainty of the other factors to be further explored.The cytochrome P450 4F2 (CYP4F2) gene, consisting of 13 exons and 12 introns and encoding 520 amino acid residues, is located on chromosome 19p13.12 in humans. Studies have shown that there are numerous single-nucleotide polymorphisms (SNPs) in the CYP4F2 gene open reading frame, such as rs2108622, rs2074...

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Section: Discussioncontrasting

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Impact of the CYP4F2 gene polymorphisms on the warfarin maintenance dose: A systematic review and meta-analysis

Sun

et al. 2016

Biomedical Reports

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“…A recent metaanalysis of 13 studies compared CYP4F2 homozygotes (CC) to carriers of CT and TT genotypes. They required 10.0% (95% CI 4.0-15.0) and 21.0% (95% CI 9.0-33.0) higher warfarin doses, respectively ( p < 0.05) [ 340 ] .…”

Section: Cyp4f2mentioning

confidence: 94%

Stroke Pharmacogenetics

Walker¹,

Stewart

Pirmohamed

2012

Stroke Genetics

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“…Several previously conducted meta-analyses show that this test has strong clinical validity and is able to provide valid information in dose estimation for patients on warfarin. [40][41][42][43][44] So, in reviewing this test, the user would continue past question 6 on clinical validity to question 7 on clinical utility. Recently conducted large randomized trials that compared testing with no testing indicate that use of this test, contrary to preliminary evidence, actually has a small to negligible effect and therefore has low clinical utility and likely would be filtered out at question 7.…”

Section: ■■ Conclusionmentioning

confidence: 99%

Improving the Efficiency and Quality of the Value Assessment Process for Companion Diagnostic Tests: The Companion test Assessment Tool (CAT)

Canestaro

Pritchard²,

Garrison³

et al. 2015

JMCP

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Influence of CYP4F2 genotype on warfarin dose requirement–a systematic review and meta-analysis

Cited by 56 publications

References 36 publications

Impact of the CYP4F2 gene polymorphisms on the warfarin maintenance dose: A systematic review and meta-analysis

Impact of the CYP4F2 gene polymorphisms on the warfarin maintenance dose: A systematic review and meta-analysis

Stroke Pharmacogenetics

Improving the Efficiency and Quality of the Value Assessment Process for Companion Diagnostic Tests: The Companion test Assessment Tool (CAT)

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