Abstract
Objectives
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.
Methods
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 CYP3A4 and ABCB1 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.
Results
The miR-142 expression levels of patients with CC allelic variant polymorphism ABCB1 3435 C>T (rs1045642) 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 ABCB1 rs4148738 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).
Conclusions
This study has assessed new potential biomarkers for rivaroxaban therapeutic drug monitoring: miR-142 and miR-39.
Funding source: Russian Science Foundation 10.13039/501100006769
Award Identifier / Grant number: 16-15-00227
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Research funding: This study is supported by the Russian Science Foundation under Project No. 16-15-00227.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: All the patients were informed about the purposes of the study and consequently have signed their “consent of the patient”. All investigations conformed to the principles outlined in the Declaration of Helsinki and were performed with permission by the responsible Ethics Committee of Russian Medical Academy of Continuous Professional Education.
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