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Association of Matrix Metalloproteinase-2 (MMP-2) and MMP-9 Promoter Polymorphisms, Their Serum Levels, and

Saeed Elahirad1, Daniel Elieh Ali Komi2, Amir Kiani3,4

  • 1Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Cardiovascular Toxicology
|November 3, 2021
PubMed

Insights

Matrix metalloproteinases (MMPs), specifically MMP-2 and MMP-9, are linked to coronary artery calcification (CAC). Genetic variations in MMP-2 and MMP-9 were associated with higher serum levels and activity of these enzymes in CAC patients, suggesting a role in calcification development.

Area of Science:

  • Cardiovascular Genetics
  • Biochemistry
  • Molecular Biology

Background:

  • Matrix metalloproteinases (MMPs) play a role in extracellular matrix remodeling.
  • Elevated serum levels and activity of MMP-2 and MMP-9 are implicated in cardiovascular diseases, including coronary artery calcification (CAC).
  • Specific single nucleotide polymorphisms (SNPs) in MMP genes may influence enzyme levels and activity, potentially impacting CAC risk.

Purpose of the Study:

  • To investigate the association between MMP-2 -1575G>A (rs243866) and MMP-9 -1562 C>T (rs3918242) SNPs and serum levels/activity of MMP-2 and MMP-9 in individuals with CAC.
  • To evaluate the relationship between these SNPs, enzyme levels/activity, and other biochemical parameters in CAC patients compared to healthy controls.

Main Methods:

  • A case-control study involving 155 CAC patients and 155 healthy controls from West Iran.
  • Genotyping of MMP-2 rs243866 and MMP-9 rs3918242 SNPs using PCR-RFLP.
  • Quantification of serum MMP-2 and MMP-9 levels by ELISA and activity by gelatin zymography.
  • Measurement of various serum biochemical parameters and blood pressure.

Main Results:

  • Serum levels and activity of both MMP-2 and MMP-9 were significantly higher in CAC patients compared to controls (P < 0.001).
  • Carriage of the A allele in MMP-2 rs243866 and the T allele in MMP-9 rs3918242 were associated with increased MMP-2 and MMP-9 serum levels and activity, respectively.
  • These genetic variants may act as risk factors, potentially predisposing individuals to CAC through enhanced extracellular matrix degradation.

Conclusions:

  • The study identifies a significant association between specific SNPs in MMP-2 and MMP-9 genes and higher serum levels and activity of these enzymes in individuals with CAC.
  • These findings suggest that MMP-2 rs243866 and MMP-9 rs3918242 variants may contribute to the pathogenesis of coronary artery calcification.
  • Targeting MMP pathways or considering these genetic markers could be relevant for understanding and managing CAC.
Keywords:
Coronary artery calcificationMMP-2MMP-9Polymorphism

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