Investigation of the frequency of VKORC1 gene polymorphisms in patients treated with warfarin in Rafsanjan city
Investigation of the frequency of VKORC1 gene polymorphisms in patients treated with warfarin in Rafsanjan city
Shima Mirzaie Parsa,1Mohsen Farzali,2Mohammad Javad Soltani Banavandi,3,*
1. 1. PhD. student in molecular genetics, Department of Biology, Islamic Azad University, Damghan branch, Damghan/Iran 2. 2. Department of Microbiology, Islamic Azad University, Kerman Branch, Kerman/Iran 3. 3. Faculty of Medicine, Islamic Azad University, Kerman Branch, Kerman/Iran
Introduction: For more than 50 years, warfarin remained the main oral anticoagulant in patients with heart valve implants, atrial fibrillation, pulmonary embolism, thrombosis or thromboembolism, and dilated cardiomyopathy worldwide. Variability in response to warfarin is one of the main obstacles to its use in clinical practice. The required dose of warfarin varies between patients by up to 30-fold, and in general, women require a lower dose than men. In general, the bleeding complication during warfarin treatment is the most common adverse drug reaction with fatal or debilitating consequences, its overdose often leads to bleeding, and its underuse puts patients at high risk of thrombotic events. Warfarin is fundamentally affected by drug interactions, alcohol consumption and some nutritional supplements. In several studies, it was found that the intake of vitamin K is related to the dose. In addition, the required dose of warfarin in different people is also influenced by non-genetic factors. such as age, gender, weight, race, diet, height, smoking, drug use, and genetic factors such as: Two genes (CYP2C9 and VKORC1),)Cytochrome P-450 family 2, subfamily C, polypeptide 9 (CYP2C9) and vitamin K epoxide reductase complex, and subunit 1 (VKORC1) genes and VKORC1 genotypes(.Clinically, the optimal dose is estimated using blood coagulation tests, usually the international normalized ratio (INR). Drug metabolism varies from one patient to another due to genetic differences. The first clues to a genetic factor in this variation appeared in the 1990s. Currently, genetic differences can explain about 50% of the interindividual variability in warfarin treatment. Each population has its own gene polymorphism, which is considered as a determining factor in drug metabolism. Overall, VKORC1 variants could explain approximately 20-30% of the variation in warfarin dose. As a result, haplotype maps of common VKORC1 SNPs were created. The present study examined the frequency of VKORC1 gene polymorphisms in patients treated with warfarin in Rafsanjan city.
Methods: In this cross-sectional study, determination of the polymorphism genotype -1369G>A was performed by PCR-RFLP method on 113 patients taking warfarin. Statistical analysis was done with SPSS version 25 software to check the relationship between the demographic data of the patients and the amount of warfarin consumption.
Results: After comparing the average dosage of warfarin, no statistically significant difference was observed in terms of age and gender in relation to this polymorphism, but genotype AA has the lowest and GG the highest dosage of warfarin in they showed the patients.
Conclusion: Optimizing the appropriate dose of warfarin for each person based on genetic and environmental factors, especially in the initial stage of use, leads to a reduction in the side effects of this drug and, as a result, a reduction in treatment costs for patients and hospitals. The present study showed that there is a significant relationship between VCORC1 polymorphisms and sensitivity to warfarin and side effects in patients treated with warfarin in Rafsanjan city. Despite achieving a statistically significant result in the identification of different polymorphisms, more studies on the effect of gene variants on drug consumption among patients should be done, because the identification of these variants and their effects may be used as an effective factor in dose estimation. In general, it can be concluded that the frequency of CYP2C9 and VKORC1 genes is different in different populations. Considering the role of CYP2C9 and VKORC1 genes, it can be stated that these two genes are more related to the changes of polymorphisms among patients and play an important role in determining the dose of warfarin used for treatment in each specific patient. Estimating the appropriate doses of warfarin to administer can help reduce the risk of over- or under-anticoagulation and subsequently the risk of thromboembolism or bleeding.