Association of VKORC1 and CYP2C9 single-nucleotide polymorphisms with warfarin dose adjustment in Saudi patients.

Abstract

Despite its wide usage, warfarin therapy remains challenging due to its narrow therapeutic index, inter-individual response variability, and risk of bleeding. Previous reports have suggested that polymorphisms in VKORC1 and CYP2C9 genes could influence warfarin therapy. Herein, we investigated whether VKORC1-1173C>T, CYP2C9*2, and CYP2C9*3 gene polymorphisms are associated with warfarin dose adjustment and related bleeding events. This cross-sectional study was conducted on Saudi adults receiving warfarin for more than 1month. Their demographics and relevant clinical data were obtained. Genotyping for VKORC1-1173C>T, CYP2C9*2, and CYP2C9*2 genotypes was performed. Patients who are homozygous for the mutant T allele VKORC1 T/T required the lowest warfarin daily maintenance dose, compared to VKORC1 C/T and VKORC1 C/C. Similarly, there was a significant reduction in warfarin daily maintenance dose among CYP2C9*1/*3 and CYP2C9*1/*2 groups compared to CYP2C9*1/*1. However, we found no significant correlation between the studied polymorphisms and warfarin-associated bleeding. Similar to other populations, the VKORC1 and CYP2C9 gene polymorphisms are significantly associated with warfarin dosage in Saudi patients. The presence of at least one copy of the mutant alleles for VKORC1-1173C>T, CYP2C9*2, and CYP2C9*3 is associated with a significant reduction in warfarin maintenance dose.