Genetic variant in the promoter region of microRNA‑137 reduces the warfarin maintenance dose in patients with atrial fibrillation.

A substantial body of research has confirmed that Vitamin K epoxide reductase complex subunit 1 (VKORC1) plays a role in contributing to the high interpatient variability in the warfarin maintenance dose. The aim of the present study was to examine the impact of SNPs of miR‑137 on the warfarin maintenance dose. Computational analysis and luciferase assay were used to search the targets of miR‑137, and luciferase assay was also used to confirm the effect of the polymorphisms on the transcription of the promoter. The regulatory relationship between miR‑137 and VKORC1 was detected using real‑time PCR. We then performed statistical analysis to find the warfarin maintenance dose in the different groups. A total of 155 subjects were enrolled in our research, and the characteristics of the patients were collected. Using computational analysis, we identified that miR‑137 binds to the VKORC1 3'untranslated region (3'UTR) and regulates the expression of VKORC1. This hypothesis was confirmed by luciferase reporter assay as miR‑137 significantly reduced the VKORC1 3'UTR luciferase activity, while the luciferase activity of mutant VKORC1 3'UTR was similar to the scramble control. According to the result of the luciferase reporter assay, we found that miR‑137 SNP with the presence of the A allele apparently reduced the luciferase activity. Using real‑time PCR, we revealed that miR‑137 negatively regulated the expression of VKORC1 in a concentration‑dependent manner in liver cells. Furthermore, no difference was noted regarding the warfarin maintenance dose between the different age or gender groups, and furthermore AC + AA carriers showed a markedly higher warfarin maintenance dose than CC carriers. These findings collectively provide support that VKORC1 is a direct target of miR‑137 and the miR‑137 rs2660304 polymorphism is associated with warfarin maintenance dose in patients with atrial fibrillation. The rs2660304 polymorphism is a potential biomarker for predicting the clinical efficacy of warfarin in these patients.