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Poster Networking

Diagnostics, OMICs and Advanced Technologies

PB1141 - Association of CYP2C9*2,*3 or VKORC1 c.−1639 G>A genetic variants with bleeding toxicity in patients taking warfarin: Meta-analysis

Tuesday, June 25, 2024
13:45 – 14:45 ICT
Room: Exhibition Hall

    Presenting Author(s)

  • Mohitosh Biswas, PhD

    Associate Professor
    Department of Pharmacy
    Rajshahi, Rajshahi, Bangladesh

    • Co-Author(s)

  • CS

    Chonlaphat Sukasem

    Professor
    Department of Pathology, Faculty of Medicine, Division of Pharmacogenomics and Precision Medicine, Mahidol University
    Bangkok, Krung Thep, Thailand

  • ME

    Maliheh Ershadian

    PhD student
    Department of Pathology, Faculty of Medicine, Division of Pharmacogenomics and Precision Medicine, Mahidol University
    Bangkok, Krung Thep, Thailand

Background: Safety of warfarin therapy may be affected by the genetic variability of CYP2C9 or VKORC1. Patients may be at increased risk of bleeding toxicity if carrying CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910) or VKORC1c.-1639G>A (rs9923231) genetic variants. There is scarcity of study assessing aggregated risk of bleeding toxicity in patients carrying these genetic variants, also taking warfarin.

Aims: It was aimed to assess aggregated risk of bleeding toxicity for patients taking warfarin, also carrying CYP2C9*2,*3 or VKORC1c.-1639G>A genetic variants.

Methods: Literature was searched in different databases following PRISMA guidelines from the inception to December 15, 2023. Odd ratios (ORs) were calculated using RevMan software where p< 0.05 was set statistical significance.

Results: In total, 25 studies consisting of 6,294 patients were included in this meta-analysis. Patients carrying genotypes combining with the CYP2C9*2 and *3 alleles treated with warfarin were associated with 92% significantly increased risk of bleeding toxicity compared to the patients with wild type genotype (OR 1.92; 95% CI 1.62-2.27; p< 0.00001). However, subgroup analysis revealed that the bleeding risk was striking in American patients (OR 2.34; 95% CI 1.69-3.23; p< 0.00001), followed by Asian patients (OR 2.02; 95% CI 1.52-2.67; p< 0.00001) compared to European patients (OR 1.57; 95% CI 1.18-2.09; p=0.002). It was also found that patients with the VKORC1 AG/AA genotypes were associated with 55% significantly increased risk of bleeding toxicity compared to the patients with VKORC1 GG genotype (OR 1.55; 95% CI 1.20-2.00; p=0.0009).

Conclusion(s): This study identified CYP2C9*2,*3 or VKORC1c.-1639G>A as the genetic risk factors for bleeding toxicity in patients taking warfarin after pooling the results from 25 studies. Bleeding risk was much higher in both American and Asian patients compared to European patients. Findings of this analysis suggest to use alternative anticoagulants in these patients, not affected by the CYP2C9 or VKORC1 genetic variants to avoid bleeding toxicity.