Evaluation of a warfarin dosing algorithm including CYP2C9, VKORC1, and CYP4F2 polymorphisms and non-genetic determinants for the Iranian population

Farajzadeh-Dehkordi, Mahvash; Samiee-Rad, Fatemeh; Farzam, Seyed Saeed; Javadi, Amir; Cheraghi, Sara; Hamedi-Asl, Dariush; Rahmani, Babak

doi:10.1007/s43440-023-00476-2

Cited by 1 publication

(1 citation statement)

References 38 publications

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“…A total of 1726 candidate studies were screened. Of these studies, 33 focused on CYP2C9 rs1057910 [11,[26][27][28][29][30][31][32][33][34][35][36][37][38][39][40] and VKORC1 rs9923231 [7,11,12,29,[33][34][35][36][37][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] polymorphisms with warfarin dosage requirement; 12 met the inclusion criteria on the susceptibility of CYP2C9 [18,32,34,[56][57][58][59] and VKORC1 [34,49,56,...…”

Section: Search Strategy and Study Selection Criteriamentioning

confidence: 99%

Association between CYP2C9 and VKORC1 genetic polymorphisms and efficacy and safety of warfarin in Chinese patients

Zhang,

Zhao,

Zhong

et al. 2024

Pharmacogenetics and Genomics

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Objectives Genetic variation has been a major contributor to interindividual variability of warfarin dosage requirement. The specific genetic factors contributing to warfarin bleeding complications are largely unknown, particularly in Chinese patients. In this study, 896 Chinese patients were enrolled to explore the effect of CYP2C9 and VKORC1 genetic variations on both the efficacy and safety of warfarin therapy. Methods and results Univariate analyses unveiled significant associations between two specific single nucleotide polymorphisms rs1057910 in CYP2C9 and rs9923231 in VKORC1 and stable warfarin dosage (P < 0.001). Further, employing multivariate logistic regression analysis adjusted for age, sex and height, the investigation revealed that patients harboring at least one variant allele in CYP2C9 exhibited a heightened risk of bleeding events compared to those with the wild-type genotype (odds ratio = 2.16, P = 0.04). Moreover, a meta-analysis conducted to consolidate findings confirmed the associations of both CYP2C9 (rs1057910) and VKORC1 (rs9923231) with stable warfarin dosage. Notably, CYP2C9 variant genotypes were significantly linked to an increased risk of hemorrhagic complications (P < 0.00001), VKORC1 did not demonstrate a similar association. Conclusion The associations found between specific genetic variants and both stable warfarin dosage and bleeding risk might be the potential significance of gene detection in optimizing warfarin therapy for improving patient efficacy and safety.

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