Pharmacogenetics Study of Warfarin by Genotyping of CYP2C9 and VKORC1 Polymorphism to Determination of Sensitivity and Resistance to Warfarin in the Population of Southern Iran

Since 1950, warfarin has been widely used as an anticoagulant medication for the prevention and treatment of thromboembolism. Various factors such as age, weight, diet, and genetic factors such as CYP2C9 and VKORC1 genes are involved in determining the dose of warfarin. This study was conducted to evaluate common polymorphisms in patients treated with warfarin.

The present cross-sectional study was conducted in the laboratory of Shahid Dastghib Hospital in Shiraz, Iran, in 2019. A total of 99 patients were selected for this study. Patients were receiving warfarin for various reasons, including heart problems. CYP2C9 and VKORC1 gene polymorphisms were investigated by a multiplex PCR method.

The haplotype frequencies of CYP2C9 alleles with *1*1, *1*3, *2*3, and *3*3 combinations were 1, 9.1, 19.2, and 70.2 percent, respectively. Among VKORC1 -1639G> A gene, allele GA, by 52.5%, was most frequent, followed by GG and AA with 34.3%, and 13.1% respectively.

The results showed a significant effect of CYP2C9 and VKORC1 gene polymorphisms on the required starting dose of warfarin to maintain INR in the range of 2-3. The CYPC2CP * 3*3* and VKORC1 -1639 G>A alleles were the most common polymorphisms in the studied population. The combination of age, weight, and haplotype genotypes of CYP2C9 and VKORC1 was the best predictive value. We can calculate the weekly dose of warfarin with the regression equation and help determine the starting dose of this drug for people with similar conditions.