تأثير التعددات الشكليّة الوحيدة النكليوتيد في جيني CYP2C9 على التغيّرات في جرعة الوارفارين

Investigating the Effect of CYP2C9 Polymorphisms on Warfarin Dose Variations

ABSTRACT
Background: Although one of the most popular anticoagulants utilized today is Warfarin, it displays considerable inter-individual variability due to genetic, environmental, or dietary factors. Among the genetic factors, polymorphisms in the CYP2C9 gene, which encoding the primary enzyme responsible for warfarin metabolism, have been shown to influence the required maintenance dose.
Aim of study: This study aimed to investigate the effect of CYP2C9*2 (rs1799853) and CYP2C9*3 (rs1057910) polymorphisms on the weekly warfarin dose among patients with mechanical heart valves receiving anticoagulation therapy. In addition, we aimed to evaluate the impact of demographic and clinical variables—including age, body weight, INR, and platelet count (PLT)—on warfarin dosing in this specific patient population.
Methods: A cross sectional observational study was conducted on 97 patients (both male and female) who were receiving warfarin therapy and had been on treatment for at least three months while maintaining a stable anticoagulation status. Data were collected between September 2024 and January 2025. During this period, each patient’s international normalized ratio (INR) was measured three times to confirm stability. Demographic and clinical data—including age, sex, body weight, INR values, and platelet count (PLT)—were collected and subjected to statistical analysis. Genotyping at the selected loci was performed using allele specific polymerase chain reaction (AS PCR) techniques.
Results: A total of 97 patients were included in this study, comprising 39.2% males (n = 38) and 60.8% females (n = 59).
The findings showed that the rs1799853 and rs1057910 variants had significant moderate correlations with weekly warfarin dose (p < 0.05), suggesting that carriers of the mutant alleles in rs1799853 (T) and rs1057910 (C) required lower doses compared to wild type carriers.
Moreover, there was a significant negative correlation between age and weekly warfarin dose (p < 0.05). Conversely, body weight demonstrated a significant positive correlation with weekly warfarin dose (p < 0.05). However, no significant associations were found between weekly warfarin dose and PLT count, INR, or sex (p > 0.05).
The results of the multiple linear regression analysis indicated that the CYP2C9 diplotype had the strongest influence on weekly warfarin dose (B = –3.65, p < 0.05), followed by body weight (B = 0.16, p < 0.05) and age (B = –0.12, p < 0.05), respectively.
Conclusion: This study demonstrated that patients carrying the CYP2C9*2/*2 and *2/*3 genotypes required significantly lower weekly doses of warfarin, with average doses of 23.5 mg and 19.5 mg, respectively. These findings highlight the importance of pharmacogenetic analysis, particularly of these SNPs, in optimizing warfarin dosing. Moreover, integrating demographic factors such as age, sex, and body weight with pharmacogenetic data is essential to further improve treatment outcomes by enhancing warfarin efficacy and minimizing adverse effects.