Genetic risk assessment towards warfarin application: Saudi Arabia study with a potential to predict and prevent side effects.

Author information

1: Department of Pharmacy Practice, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Saudi Arabia.

Abstract

Warfarin doses are greatly affected by polymorphism altering cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) gene. This study evaluated the prevalence of alleles (either single or double) and carriers of single nucleotide polymorphisms (SNPs) in both genotypes CYP2C9 and VKORC1 in alkharj area, Saudi Arabia and its association with warfarin use risk. Total 112 samples were collected and genotyped using FlexiGene DNA Kit for isolation and StepOnePlus Real-Time PCR System by TaqMan allelic discrimination methods. The results indicated the frequency of 11%, 8% and 45% for CYP2C9 *2 *3 and VKORC1-1639 G > A polymorphism. And as a combination genotype it was 15.18% For both CYP2C9 and VKORC1 polymorphism, 27.67% for CYP2C9 and 42.86% for VKORC1. Non-carriers rate came to be at 30.3%. According to previously published dosing changes in warfarin for polymorphism carriers (single-double-triple). The predicted warfarin doses reduction in order of 1-1.6, 2-2.9, 2.9-3.7 mg/day. It was found that 72.3% of the study population was carrier of a type of polymorphism, 15.18% for two types of polymorphisms. These findings predict changes in warfarin metabolism and eventually dosing alteration among patients on warfarin. Both genotypes (CYP2C9 and VKORC1) require different dosing of warfarin than non-carriers in order to minimize the risk of warfarin overdosing and avoidance of the drug-related problems (DRPs).