Genetic Determinants of Cytochrome-P450 2C9 (CYP2C9) in Response to Warafarin during Initial Anticoagulation
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- Category: Vol. 85, September 2017
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Genetic Determinants of Cytochrome-P450 2C9 (CYP2C9) in Response to Warafarin during Initial Anticoagulation, MOHAMMED A. BASHEER, MOSTAFA M. AMER, HOSSAM H. ALI, HOSNI B. HAMED and MOHAMMED S. ALLAM
Abstract
Purpose: Warfarin is an anticoagulant that acts through vitamin K-dependent clotting factors inhibition. It is used in the prevention and treatment of thrombotic disorders. The cytochrome P450 superfamily (CYP) is a large and diverse group of enzymes that form the major system for metabolizing drugs. The CYP genes are often polymorphic and can result in reduced, absent, or increased drug metabolism. This study was conducted to find out the effect of genetic polymorphisms of CYP2C9 gene on the modulation of warfarin dose require-ments.
Patients and Methods: The current study was performed on 50 patients who were treated with warfarin and visiting outpatient clinics and cardiology ICU of Al-Azhar University Hospital and South Egypt Cancer Institute, Assiut from De-cember 2013 to December 2014 to monitor their International Normalized Ratio (INR) and 20 apparently healthy volunteers that were taken as control. Genotyping assay for detection of CYP2C9 polymorphisms using multiplexed lightmix real time PCR was done.
Results: Among the 50 studied patients, 78% of cases were Cyp2C9*1 (wild type). 16% were Cyp2C9*2 (heterozy-gous type), and 6% were Cyp2C9*3 (heterozygous type). A highly statistically significant difference was found between different genotypes in mean values of 1st reading of INR level. Heterozygous genotypes (CYP2C91*2 & CYP2C91*3) show higher mean of first INR reading than wild genotype (CYP2C91 * 1) p-value (0.019). A highly statistically significant difference was found between genotype groups in warfarin dose on follow-up, p-value (0.001). CYP2C91*1 wild genotype was needed the highest maintenance warfarin dose (4.14±1.77) then CYP2C91 *2 heterozygous genotype (2.31±0.75) and then CYP2C91*3 heterozygous genotype was needed the lowest warfarin maintenance dose (1.67±0.29). Also, it was found that there was high significant relation between bleeding complication and genotype (CYP2C91 *3). p-value (0.001).
Conclusion: This study showed that patients with CYP2C9 (1*1) (wild genotype group) had low initial INR so we should give those patients higher doses of warfarin at initial time than heterozygous genotype group. Patients with CYP2C9 (1*2) (heterozygous genotype group) had intermediate initial INR. Patients with CYP2C9 (1*3) (heterozygous genotype group) had highest initial INR so we should give them lowest dose of warfarin at initial time of treatment. Bleeding com-plication is more common with genotype 3 CYP2C9 (1*3). On follow-up CYP2C9 (1*1) genotype patients' needs a highest doses of warfarin then patients with genotype CYP2C9 (1*2) then patients with genotype CYP2C9 (1*3).