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Genetic Associations of Plasminogen Activator Inhibitor-1-Related miRNA Variants with Coronary Artery Disease

Yong Hyun Ha1, Jung Hoon Sung2, Chang Soo Ryu1

  • 1Department of Biomedical Science, College of Life Science, CHA University, Seongnam 13488, Republic of Korea.

International Journal of Molecular Sciences
|November 9, 2024
PubMed

Insights

Polymorphisms in microRNA-30c (miR-30c) are linked to coronary artery disease (CAD) susceptibility in Koreans. Specific miR-30c and miR-143 genotypes increase CAD risk, especially with metabolic syndrome or diabetes.

Area of Science:

  • Genetics and Molecular Biology
  • Cardiovascular Disease Research
  • Biomarker Discovery

Background:

  • Coronary artery disease (CAD) results from plaque buildup in coronary arteries, impeding blood flow.
  • PAI-1 gene polymorphisms are linked to CAD, but the role of its 3'-untranslated region and interacting microRNAs (miRNAs) is understudied.
  • Understanding post-transcriptional regulation via miRNA-gene interactions is crucial for CAD research.

Purpose of the Study:

  • To investigate the association between miRNA polymorphisms targeting the PAI-1 3'-untranslated region and CAD risk in the Korean population.
  • To explore the combined effects of specific miRNA genotypes and clinical factors on CAD susceptibility.
  • To identify potential miRNA-based prognostic biomarkers for CAD.

Main Methods:

  • Genotyping of five polymorphisms in four miRNAs targeting the PAI-1 3'-untranslated region using real-time PCR and TaqMan assays.
  • Analysis of genotype and allele combinations for associations with CAD.
  • Evaluation of synergistic effects of metabolic syndrome and diabetes mellitus with miRNA polymorphisms on CAD risk.

Main Results:

  • The mutant genotype of miR-30c rs928508 (A > G) showed a strong association with increased CAD susceptibility.
  • Combined genotypes (homozygous mutant miR-30c rs928508 and wild-type miR-143 rs41291957) and allele combinations (mutant miR-30c rs928508 and wild-type miR-143 rs41291957) significantly increased CAD risk.
  • Metabolic syndrome and diabetes mellitus exhibited synergistic effects with miR-30c rs928508 on CAD risk.

Conclusions:

  • The miR-30c rs928508 polymorphism is a significant risk factor for CAD in the Korean population.
  • Combinations of specific miRNA polymorphisms and clinical factors like metabolic syndrome and diabetes can enhance CAD risk prediction.
  • These findings support the use of miRNA polymorphisms as potential prognostic biomarkers for CAD.

Keywords:
coronary artery diseasemicroRNAplasminogen activator inhibitor-1

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