Impact of CYP3A4 rs2242480 Gene Polymorphism on Rivaroxaban Plasma Level Concentration and Bleeding Risks among Iraqi Patients with Atrial Fibrillation

Abstract

Background:

A prevalent cardiac arrhythmia that dramatically raises the risk of stroke and systemic embolism is atrial fibrillation (AF). Moreover, because of their known pharmacokinetic and pharmacodynamic profile, convenience of administration, and fixed-dose administration, anticoagulants, such as rivaroxaban, are important and widely used to treat atrial fibrillation and prevent stroke. However, various factors, including genetic variations in the drug's metabolism, may have a role in the variation responsible for the response's interindividual heterogeneity. Cytochrome P450 3A4 is the major enzyme responsible for the metabolism of rivaroxaban. So, the polymorphisms on this enzyme (such as rs2242480) may change the metabolism, and then a change in plasma concentration may increase or decrease bleeding events.

Study objectives:

This study aims to determine the frequency of the CYP3A4 single-nucleotide polymorphism (SNP) rs2242480 in this cross-sectional study to examine the effect of the polymorphism on the plasma concentration of rivaroxaban and risk of bleeding in patients with atrial fibrillation (AF) from Iraq

Patients and Methods:

This study examined the effect of the CYP3A4 rs2242480 polymorphism on the rivaroxaban plasma concentration levels in 100 Iraqi atrial fibrillation patients receiving a fixed dose of 20 mg/day. Genotyping was done with allele-specific PCR, and the plasma levels were determined with HPLC.

Results:

The genotype distributions for rs2242480 were 10% TT, 29% CT, and 61% CC (wild-type). The mean rivaroxaban concentration was greater in patients with the T allele (CT and TT) (341.60 (336.80) ng/mL for CT and 399.00 (349.78) ng/mL for TT) than in patients with the CC genotype (152.60 (344.40) ng/mL). Still, this difference was not statistically significant (p = 0.248). Clinical and biochemical indicators did not significantly correlate with genotype, so bleeding events were reported in 10% of patients; there was also no significant association between bleeding events and CYP3A4 rs2242480 genotype. The bleeding episodes were generally mild and did not result in significant complications.

Conclusion:

In Iraqi individuals with atrial fibrillation, the CYP3A4 rs2242480 polymorphism has no recognized effect on rivaroxaban plasma levels or bleeding episodes. These findings imply that rivaroxaban treatment in this cross-sectional study may not require routine genotyping for this variant. Further extensive research and genetic analyses are needed to validate these results and investigate additional genetic factors impacting rivaroxaban metabolism.