Scientific Poster Session III - Late-Breaking Original Research

Abstract

Warfarin dosing is challenging due to its narrow therapeutic window and inter-individual response variations, influenced by demographic, environmental, and genetic factors, especially single nucleotide polymorphisms (SNPs) in genes related to warfarin’s mechanism and metabolism.

Research Question or Hypothesis:

This study aimed to assess the frequency of CYP2C9 *2, CYP2C9 *3, and VKORC1 (-1639G/A) alleles in Syrian patients on warfarin and identify factors affecting warfarin responsiveness.

Study Design: This cross-sectional cohort study included 93 warfarin-treated patients. Data on demographics, smoking, medical history, warfarin dose, co-medications, International Normalized Ratio (INR) values, and hemorrhagic events were collected.

Methods: Genotypes were identified by sequencing CYP2C9 and VKORC1 genes, and their effects on warfarin dose and adverse effects were analyzed. A dosing algorithm was developed using stepwise multiple linear regression.

Results:

Our study found that only 11.8% of participants had normal genotypes for both genes. The frequencies of VKORC1 (-1639G/A), CYP2C9*2, and CYP2C9*3 were 46.2%, 13.97%, and 11.8%, respectively. Patients with the wild type allele required a median weekly warfarin dose of 50.3 mg, while those with one variant needed 34.5 mg (P = 0.032). Four variables including VKORC1 genotype, CYP2C9 genotype (wild type vs. mutant), age and smoking status are found to have a relevant influence on warfarin dosage variability. Multivariate analysis produced the equation:

Weekly Dose of Warfarin=61.01-(6.12×VKORC1 genotype)-(6.12×CYP2C9 genotype)-(0.31×Age)+(15.96×Smoking)

Genetic factors explained 17.4% of dose variance (P = 0.01), and clinical factors explained 22% (P < 0.01). Hemorrhagic incidents were higher in patients with allele *2/*3 (36.4%) compared to wild type (16%) (P = 0.02), but VKORC1 genotype was not significantly associated with bleeding P= 0.21.

Conclusion: Both genetic and clinical factors influenced the weekly warfarin dose. VKORC1 was more associated with a decreased dose than *2/*3 alleles, which were linked to higher sensitivity and bleeding risk, necessitating dose reduction. These findings support personalized warfarin management in the Syrian population.

Presenting Author

Authors