Influence of vitamin k epoxide reductase complex 1 polymorphism on warfarin therapy in a cohort study of Saudi patients

Abstract

Background and Objective: Precision medicine is a new field of medicine aimed to individualize patient therapy through identifying patient’s genotype specifically with narrow therapeutic index medications. Warfarin is a widely used vitamin K antagonists (VKA) that showed great inter- and intra-individual dose variability depending on many genetic and non-genetic factors. This study was designed to assess the effect of 1173C>T SNPs of vitamin K epoxide reductase complex 1 (VKORC1) on the dose variability and patient response to warfarin in a cohort of Saudi population. Methodology: Initially, 190 patients from internal medicine and cardiology units of Prince Sattam bin Abdulaziz University “PSAU” hospital and Prince Sultan Military hospital were recruited over 12 months. Only 175 accepted to take part in this study. Patients who failed to be followed up were excluded (n = 11). Genomic DNA of all patients was isolated and quantified, then genotyped for rs9934438 variants (6484C>T or 1173C>T SNP) of VKORC1 gene by TaqMan allelic discrimination genotyping. The primary outcome was the time patients’ INR value in therapeutic range (TTR). Results: The study participants (n = 164) were on chronic warfarin therapy for different indications. The minor allele frequency (MAF) of 1173C>T SNP in Saudi patients (0.259) is greatly different from other ethnic groups particularly Asian (0.90). Patients who have either genotype variant alleles showed significantly less warfarin dose. TTR was significantly lower in T/T homozygous genotype (68.4%) than C/C wild-type or heterozygous C/T genotype. Conclusion: VKORC1 1173C>T SNP is associated with lower warfarin dose in a cohort of Saudi patient and screening for this SNP tend to identify patients at risk of bleeding or patients that may have higher INR target.