Influence of CYP2C9 and VKORC1 genotypes on the risk of hemorrhagic complications in warfarin-treated patients: A systematic review and meta-analysis

Yang, Jie; Chen, Yanming; Li, Xiaoqi; Wei, Xiaowen; Chen, Xi; Zhang, Lanning; Zhang, Yuxiao; Xu, Qiang; Wang, Hongjuan; Yang, Li; Lu, Caiyi; Wei, Chen; Zeng, Changqing; Yin, Tong

doi:10.1016/j.ijcard.2013.07.151

Cited by 91 publications

(71 citation statements)

References 72 publications

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“…Using a stepwise method, VKORC1-1639 G > A SNP, age and weight were revealed as factors associated with interindividual variability in the daily warfarin dose. Although CYP2C9 genetic variants have been recognized as key factors affecting daily warfarin dose in other research, 23 this was not the case in the present study. This discrepancy between results may be due to the fact that: (I) allele frequency of the CYP2C9*3 genotype, which affects CYP2C9 enzyme activity, is too low to cause significant distinction in the Chinese population, and (II) the sample size of the present study population was not sufficient to detect significant differences.…”

Section: Discussioncontrasting

confidence: 65%

Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene polymorphisms in Chinese patients

Jin

Zhang

et al. 2013

J Int Med Res

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Objective: To investigate the prevalence and implication of cytochrome P450, family 2, subfamily C, polypeptide 9 (CYP2C9) variants and vitamin K epoxide reductase complex, subunit 1 (VKORC1)-1639 G > A polymorphisms in Chinese patients receiving warfarin therapy. Methods: Chinese Han patients requiring oral warfarin therapy were consecutively enrolled. Correlations between CYP2C9*1, *2, *3, *4, *5 variants and VKORC1-1639 G > A polymorphisms, fourth-day international normalized ratios (INRs) and warfarin maintenance dose were investigated. Results: Out of 101 patients, there were no significant differences in fourth-day INR or warfarin daily maintenance doses between patients with CYP2C9*1*1 and CYP2C9*1*3 genotypes. Patients with the VKORC1-1639 AA genotype had a higher fourth-day INR (1.87 AE 0.14) than those with the VKORC1-1639 AG genotype (1.32 AE 0.15). Warfarin maintenance dose for patients with the VKORC1-1639 AA genotype (2.40 AE 0.70 mg/day) was significantly lower than for patients with the VKORC1-1639 AG genotype (4.83 AE 0.70 mg/day). Conclusions: Unlike Caucasian populations, VKORC1-1639 G > A polymorphisms in the Chinese population may be the dominant genetic factors associated with warfarin response variability.

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Section: Discussioncontrasting

confidence: 65%

Variability of warfarin dose response associated with CYP2C9 and VKORC1 gene polymorphisms in Chinese patients

Jin

Zhang

et al. 2013

J Int Med Res

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“…Two systematic reviews have shown that the carriage of the CYP2C9*3 allele seems to increase the risk of warfarin-related bleeding [14,23]. Interestingly, a recent study has suggested that the risk of lobar cerebral hemorrhage in patients on warfarin is increased in apolipoprotein E (APOE) e2 and e4 carriers, but there was no interaction between APOE and warfarin [24].…”

Section: Pharmacology Of Warfarinmentioning

confidence: 99%

Oral anticoagulation: a critique of recent advances and controversies

Pirmohamed

Kamali

Daly

et al. 2015

Trends in Pharmacological Sciences

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“…Although efforts are dedicated to explore whether CMBs can be a potential radiological marker that guide antithrombotic therapy, treatment decision should always take into account other underlying risk factors. A reliable risk model, incorporating imaging hemorrhagic markers (CMBs, white matter hyperintensities, cortical superficial siderosis, etc), genetic factors (apolipoprotein E, vitamin K epoxide reductase complex subunit 1, cytochrome P450 2C9, etc), 56 and clinical risk factors (age, hypertension, diabetes mellitus, end-stage renal disease, etc) may be helpful for decision making on specific patients. Some existing risk scores Figure 2.…”

Section: Recommendations and Future Directionsmentioning

confidence: 99%