MicroRNAs as novel biomarkers for rivaroxaban therapeutic drug monitoring

• Published in: Drug metabolism and personalized therapy
• Main Authors: Rytkin, Eric, Bure, Irina V, Bochkov, Pavel O, Akmalova, Kristina A, Mirzaev, Karin B, Cherniaeva, Marina S, Ostroumova, Olga D, Smirnov, Valery V, Grishina, Elena A, Saribekian, Anna G, Sychev, Igor N, Sychev, Dmitry A
• Format: Journal Article
• Language: English
• Published: Germany 13.08.2021
• Subjects: atrial fibrillation; miRNA; polymorphism; rivaroxaban; biomarker
• ISSN: 2363-8915

The aim of this study is to assess micro-RNAs miR-142 and miR-39 as potential biomarkers for drug-monitoring of rivaroxaban among elderly patients with atrial fibrillation. The study involved 57 patients with median (ME) age 87 years [80-94 years old] with nonvalvular atrial fibrillation admitted to a multidisciplinary hospital in Moscow. High-performance liquid chromatography with mass-spectrometry detection (HPLC-MS) was carried out to measure rivaroxaban concentrations. Carriership of and was detected. MiRNA expression levels were measured. The activity of CYP3A4 isoenzyme was measured as the ratio of the concentrations of 6β-hydroxycortisol and cortisol. The miR-142 expression levels of patients with CC allelic variant polymorphism were significantly higher compared to CT and TT variants 31.69 ± 1.60 vs. 34.06 ± 1.66 vs. 33.16 ± 1.77 (p=0.021). Carriers of TT allelic variant polymorphism had a higher concentration of the 6-beta-hydroxycortisol in urine compared to CC and CT variants 3,467.35 ± 1,055.53 vs. 3,453.52 ± 1,516.89 vs. 2,593.30 ± 1,172.52 (p=0.029). As for CYP3A4*22, the carriers of CC allelic variant had higher prothrombin time 14.10 ± 2.17 vs. 11.87 ± 0.60 and INR 1.31 ± 0.20 vs. 1.1 ± 0.06 but lower Quick's value 74.52 ± 16.84 vs. 97.55 ± 10.54 (p=0.059). A positive correlation between the Ct miR-142 and the aPTT p=0.019 was noted. Also miR-142 has a correlation with Quick's value p=0.095. There is no statistically significant connection between miR-142 and miR-39 expression levels and the plasma concentration of rivaroxaban (b coefficient=-2.055, SE 3.952, p=0.605 and b coefficient=1.546, SE 9.887, p=0.876 in the linear regression model respectively). This study has assessed new potential biomarkers for rivaroxaban therapeutic drug monitoring: miR-142 and miR-39.