title: Prognostic role of MIR146A polymorphisms for cardiovascular events in atrial fibrillation.
abstract: 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.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Roldán
authors.forename: Ana Belen
authors.initials: AB
authors.lastname: Arroyo
authors.forename: Sallam
authors.initials: S
authors.lastname: Salloum-Asfar
authors.forename: Sergio
authors.initials: S
authors.lastname: Manzano-Fernández
authors.forename: Nuria
authors.initials: N
authors.lastname: García-Barberá
authors.forename: Francisco
authors.initials: F
authors.lastname: Marín
authors.forename: Vicente
authors.initials: V
authors.lastname: Vicente
authors.affiliation: Rocío González-Conejero, Centro Regional de Hemodonación, Ronda de Garay s/n, 30003 Murcia, Spain, Tel.: +34 968341990, Fax: +34 968261914, E-mail: rocio.gonzalez@carm.es.
authors.forename: Rocío
authors.initials: R
authors.lastname: González-Conejero
authors.affiliation: Constantino Martínez, Centro Regional de Hemodonación, Ronda de Garay s/n, 30003 Murcia, Spain, Tel.: +34 968341990, Fax: +34 968261914, E-mail: constant@um.es.
authors.forename: Constantino
authors.initials: C
authors.lastname: Martínez
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000737:chemistry; D001281:Atrial Fibrillation / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D015415:Biomarkers; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D015850:Interleukin-6; D008070:Lipopolysaccharides; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Atrial fibrillation; cardiovascular event; inflammation; mir-146a-5p