Relevance of genetic polymorphisms of the human cytochrome P۴۵۰ ۳A۴ in rivaroxaban-treated patients

Rivaroxaban is an anticoagulant drug that prevents forming of blood clots. In addition, it can be administered to prevent and treat thrombotic diseases such as atrial fibrillation, cardiac arrhythmia, heart valve disease, orthopedic surgery, and thrombophilia to reduce the risk of thrombosis. Various factors such as age, gender, diet, medications, and genetic factors effectively determine the dose of rivaroxaban. Genetic variability in drug-metabolizing enzymes, including the cytochrome P۴۵۰ (CYP۴۵۰) enzymes and especially CYP۳A۴, has been associated with rivaroxaban response. The current study aimed to identify the frequency of CYP۳A۴ common polymorphisms, as well as their association with rivaroxaban response in ۱۰۰ patients of Arab descent (۴۸.۶% female). CYP۳A۴ gene polymorphisms were examined by the PCR-RFLP method, and the findings were analyzed by SPSS ۱۶ software and t-test. The frequency of CYP۳A۴*۱B/*۱B, CYP۳A۴*۱B/*۱A, CYP۳A۴*۱B/*۱C, and CYP۳A۴*۱A/*۱C was ۶۷.۳۵%, ۱۰.۶۴%, ۱۹.۱۲% and ۲.۸۹%, respectively. According to our results, CYP۳A۴ *۱B/*۱B genotype was the most common, and patients with CYP۳A۴*۱B/*۱B alleles needed a higher daily dose of rivaroxaban than *۱B/*۱A, *۱B/*۱C, and *۱A/*۱C carriers (۹.۵۷ ± ۱.۵۴ mg/day, P=۰.۰۱۵). Therefore, according to the results, CYP۳A۴ gene polymorphism has an important effect on the dose of rivaroxaban required to maintain the International Normalized Ratio (INR) in the range of ۲-۳.

Keywords:

Blood Clots , Cardiovascular disease , CYP۳A۴ gene , Genetic Characteristics , Multiple Alleles