Association of MIR-499a expression and seed region variant (rs3746444) with cardiovascular disease in Egyptian patients

Acta Cardiol. 2018 Apr;73(2):131-140. doi: 10.1080/00015385.2017.1351243. Epub 2017 Aug 8.

Abstract

Background: Circulating microRNAs could be powerful markers of acute myocardial infarction (MI) and its functional genetic variants could increase susceptibility to cardiovascular disease (CVD). The current study aimed to quantify the microRNA (miR)-499a levels in serum of MI patients compared to hypertensive and healthy subjects and to investigate the association of its A/G variant rs3746444 with CVD in a sample of an Egyptian population.

Methods: Serum miR-499a relative expressions were measured in 110 acute MI patients, 76 hypertensive patients, and 121 healthy controls by Real-time quantitative polymerase chain reaction. MIR-499a genotyping was performed for an additional 107 coronary artery disease patients by Real-time allele discrimination assay.

Results: Acute MI patients showed high relative expression of miR-499a (> 105-fold, p < .001), and it was nearly undetectable in healthy controls and hypertensive patients. It showed an area under the curve of 0.953, with a sensitivity of 97.2% and a specificity of 75.0%. ST-elevation MI (STEMI) patients had higher miR-499a serum levels than patients with Non-STEMI. There was a significant association of MIR-499a variant with acute MI but not with hypertension under all genetic models tested. As a new finding, in overall and stratified analysis, the miR-499a variant was not correlated with its expression profile.

Conclusions: Circulating miR-499a levels could be a useful biomarker, discriminating acute MI within 12 hours from healthy subjects. Its variant rs3746444 A/G is associated with increased susceptibility to acute MI and CAD in Egyptian population.

Keywords: Coronary artery disease; gene expression; miR-499a; myocardial infarction; polymorphism.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / genetics*
  • Cardiovascular Diseases / metabolism
  • Egypt / epidemiology
  • Female
  • Gene Expression Regulation*
  • Genetic Predisposition to Disease*
  • Humans
  • Incidence
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA / genetics*
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies

Substances

  • MIRN499 microRNA, human
  • MicroRNAs
  • RNA