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Prognostic role of MIR146A polymorphisms for cardiovascular events in atrial fibrillation

Vanessa Roldán, Ana Belen Arroyo, Sallam Salloum-Asfar

  • 1Rocío González-Conejero, Centro Regional de Hemodonación, Ronda de Garay s/n, 30003 Murcia, Spain, Tel.: +34 968341990, Fax: +34 968261914,

Thrombosis and Haemostasis
|July 11, 2014
PubMed

Insights

The MIR146A rs2431697 genetic variant is a prognostic biomarker for adverse cardiovascular events in atrial fibrillation patients. TT genotype carriers exhibit increased inflammation due to lower miR-146a-5p levels, increasing thrombotic risk.

Area of Science:

  • Cardiovascular Biology
  • Genetics
  • Immunology

Background:

  • Biomarkers for predicting thrombotic events in atrial fibrillation (AF) are limited.
  • MicroRNAs, particularly miR-146a-5p, are key regulators of inflammation in cardiovascular disease.
  • Functional polymorphisms in the MIR146A gene may influence cardiovascular event risk.

Purpose of the Study:

  • To evaluate the prognostic role of MIR146A polymorphisms (rs2431697 and rs2910164) in non-valvular AF patients.
  • To investigate the biological effects of these polymorphisms on inflammation and miR-146a-5p levels.
  • To assess the utility of rs2431697 as a biomarker for adverse cardiovascular events (ACE).

Main Methods:

  • Prospective study of 901 non-valvular AF patients followed for two years for ACE.
  • Genotyping for MIR146A polymorphisms rs2431697 and rs2910164.
  • In vitro studies using monocytes from healthy individuals with different rs2431697 genotypes to assess miR-146a-5p expression and inflammatory response.

Main Results:

  • Rs2910164 showed no association with ACE.
  • The rs2431697 TT genotype was significantly associated with an increased risk of ACE (HR: 1.64, p=0.017), independent of the CHA2DS2-VASc score.
  • The CHA2DS2-VASc+IL6+rs2431697 model showed improved predictive value for ACE compared to CHA2DS2-VASc+IL6 alone.
  • In vitro, TT genotype monocytes exhibited lower miR-146a-5p induction and higher IL6 mRNA expression upon inflammatory stimulation compared to CC genotype monocytes.

Conclusions:

  • MIR146A rs2431697 is a novel prognostic biomarker for predicting adverse cardiovascular events in anticoagulated AF patients.
  • The TT genotype of rs2431697 may predispose individuals to a pro-inflammatory state due to reduced miR-146a-5p levels, contributing to increased thrombotic risk.
  • These findings highlight the role of genetic variations in inflammation and cardiovascular risk stratification in AF.
Keywords:
Atrial fibrillationcardiovascular eventinflammationmir-146a-5p

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