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Thromb Haemost 2014; 112(04): 781-788
DOI: 10.1160/TH14-01-0092
Cardiovascular Biology and Cell Signalling
Schattauer GmbH

Prognostic role of MIR146A polymorphisms for cardiovascular events in atrial fibrillation

Vanessa Roldán
1   Centro Regional de Hemodonación, Hematology and Medical Oncology Unit, Hospital Universitario Morales Meseguer, IMIB, Murcia, Spain
,
Ana Belen Arroyo
1   Centro Regional de Hemodonación, Hematology and Medical Oncology Unit, Hospital Universitario Morales Meseguer, IMIB, Murcia, Spain
,
Sallam Salloum-Asfar
1   Centro Regional de Hemodonación, Hematology and Medical Oncology Unit, Hospital Universitario Morales Meseguer, IMIB, Murcia, Spain
,
Sergio Manzano-Fernández
2   Department of Cardiology, Hospital Universitario Virgen de la Arrixaca, University of Murcia, IMIB, Murcia, Spain
,
Nuria García-Barberá
1   Centro Regional de Hemodonación, Hematology and Medical Oncology Unit, Hospital Universitario Morales Meseguer, IMIB, Murcia, Spain
,
Francisco Marín
2   Department of Cardiology, Hospital Universitario Virgen de la Arrixaca, University of Murcia, IMIB, Murcia, Spain
,
Vicente Vicente
1   Centro Regional de Hemodonación, Hematology and Medical Oncology Unit, Hospital Universitario Morales Meseguer, IMIB, Murcia, Spain
,
Rocío González-Conejero   *
1   Centro Regional de Hemodonación, Hematology and Medical Oncology Unit, Hospital Universitario Morales Meseguer, IMIB, Murcia, Spain
,
Constantino Martínez   *
1   Centro Regional de Hemodonación, Hematology and Medical Oncology Unit, Hospital Universitario Morales Meseguer, IMIB, Murcia, Spain
› Author Affiliations Financial support: This work was supported by research grants from Instituto Carlos III and Fondo Europeo de Desarrollo Regional (FEDER) (PI11/00566, PI11/1256, and Red RIC RD12/0042/0050) and Fundación Española de Trombosis y Hemostasia. CM is an investigator from Fundación para la Formación e Investigación Sanitarias de la Región de Murcia. SMF has received funding for research from Sociedad Española de Cardiología.
Further Information

Publication History

Received: 29 January 2014

Accepted after major revision: 21 May 2014

Publication Date:
21 November 2017 (online)

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Summary

There are few biomarkers able to forecast new thrombotic events in patients with AF. In this framework, microRNAs have emerged as critical players in cardiovascular biology. In particular, miR-146a-5p is recognised as an important negative regulator of inflammation. This study aims to evaluate the prognostic role and biological effect of functional MIR146A polymorphisms, rs2431697 and rs2910164, in non-valvular atrial fibrillation (AF) patients under oral anticoagulation. We studied 901 patients with permanent/paroxysmal AF stabilized for at least six months. Patients were followed-up for two years and adverse cardiovascular events (ACE) were recorded. In vitro studies were performed in monocytes from healthy homozygous for the two genotypes of rs2431697. Rs2910164 had no association with ACE. However, multivariate analysis (adjusted by CHA2DS2–VASc score) revealed that rs2431697TT was associated with adverse cardiovascular events [HR: 1.64 (1.09–2.47); p=0.017]. The predictive value of usefulness of the CHA2DS2–VASc+IL6+rs2431697 for predicting ACE, was statistically better than that predicted by CHA2DS2–VASc+IL6. Functional studies showed that after 24 hours incubation, monocytes from CC individuals showed a 65 % increase in miR-146a-5p levels, while TT individuals only showed a 28 % increase. Indeed, after 24 hours of LPS activation, TT monocytes showed a higher increase in IL6 mRNA expression than CC (52 % vs 26 %). Our study established MIR146A rs2431697 as a prognostic biomarker for ACE in anticoagulated AF patients. These data suggest that TT individuals, when submitted to an inflammatory stress, may be prone to a highest pro-inflammatory state due, in part, to lower levels of miR-146a-5p.

Keywords

Atrial fibrillation - mir-146a-5p - inflammation - cardiovascular event

* RGC and CM share senior authorship.


 

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