The Relationship Between Warfarin Resistance and CYP2C9*2 and CYP2C9*3 Variations

Objective: Warfarin is one of the most widely used anticoagulants worldwide. Some patients need >15 mg/day of warfarin to get theirtherapeutic international normalized ratio (INR). This condition is known as warfarin resistance (WR). WR is related to enzyme deficiencies, which play a role in warfarin metabolism. One of the most important enzyme-related drug metabolism is the cytochrome P450, family 2, subfamily C, member 9 (CYP2C9). Therefore, this study aimed to investigate the relationship between CYP2C9 variations and WR. Methods: To find patients with WR, 650 patients who used warfarin for at least 6 months were screened. Then, patients were grouped into two according to the INR values, wherein 30 patients with INR levels not reaching the therapeutic range (<2) despite using 15 mg of warfarin per day were included in the non-responder group and 30 randomly selected patients who received low-dose warfarin, whose INR levels were within the therapeutic range (2-3), were included in the responder group. After the genomic deoxyribonucleic acid isolation from the peripheral blood, CYP2C9*2 and CYP2C9*3 variations were investigated using the real-time polym erase chain reaction. Results were statistically evaluated. Results: Heterozygous genotype of CYP2C9*3 was statistically high in responders (33.3%), whereas the wild-type genotype was statistically high in nonresponders (90%) (p<0.05). In addition, the T allele of CYP2C9*2 (18.3%) and the C allele of CYP2C9*3 (16.7%) were statistically high in responders (p<0.05). Conclusion: Patients with gene variations that reduced the CYP2C9 activity are termed poor metabolizers. These individuals metabolize warfarin more slowly and require smaller doses of the drug to reach the therapeutic INR values. Therefore, adjusting the warfarin dose is possible depending on the genotype of patients.