Impact of <i>CYP2C9</i> and <i>VKORC1</i> Polymorphisms on Warfarin Sensitivity and Responsiveness in Jordanian Cardiovascular Patients during the Initiation Therapy

• Main Authors: Laith N. AL-Eitan, Ayah Y. Almasri, Rame H. Khasawneh
• Format: Article
• Language: English
• Published: MDPI AG 2018-11-01
• Series: Genes
• Subjects: <i>CYP2C9</i>; <i>VKORC1</i>; warfarin; warfarin initiation phase of therapy; INR; pharmacogenetics study
• Online Access: https://www.mdpi.com/2073-4425/9/12/578

Warfarin is an oral anticoagulant frequently used in the treatment of different cardiovascular diseases. Genetic polymorphisms in the <i>CYP2C9</i> and <i>VKORC1</i> genes have produced variants with altered catalytic properties. A total of 212 cardiovascular patients were genotyped for 17 Single Nucleotide Polymorphisms (SNPs) within the <i>CYP2C9</i> and <i>VKORC1</i> genes. This study confirmed a genetic association of the <i>CYP2C9</i>*3 and <i>VKORC1</i> rs10871454, rs8050894, rs9934438, and rs17708472 SNPs with warfarin sensitivity. This study also found an association between <i>CYP2C9</i> and <i>VKORC1</i> genetic haplotype blocks and warfarin sensitivity. The initial warfarin dose was significantly related to the <i>CYP2C9</i>*3 polymorphism and the four <i>VKORC1</i> SNPs (<i>p</i> &lt; 0.001). There were significant associations between rs4086116 SNP and TAT haplotype within <i>CYP2C9</i> gene and rs17708472 SNP and CCGG haplotype within <i>VKORC1</i> gene and warfarin responsiveness. However, possessing a <i>VKORC1</i> variant allele was found to affect the international normalized ratio (INR) outcomes during initiation of warfarin therapy. In contrast, there was a loose association between the <i>CYP2C9</i> variant and INR measurements. These findings can enhance the current understanding of the great variability in response to warfarin treatment in Arabs.