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Matrix metalloproteinase-3 gene polymorphism (rs3025058) affects markers atherosclerosis in type 2 diabetes mellitus

Aleš Pleskovič1, Marija Šantl Letonja2, Andreja Cokan Vujkovac3

  • 11 Department of Cardiology, University Medical Centre, University of Ljubljana, Ljubljana, Slovenia.

VASA. Zeitschrift Fur Gefasskrankheiten
|May 20, 2017
PubMed
Abstract

Insights

The MMP-3 rs3025058 gene polymorphism is associated with carotid atherosclerosis progression and coronary artery disease markers in patients with type 2 diabetes mellitus (T2DM). This finding highlights a potential genetic link to cardiovascular complications in T2DM.

Area of Science:

  • Cardiovascular Genetics
  • Diabetes Mellitus Research
  • Molecular Biology

Background:

  • Type 2 diabetes mellitus (T2DM) is a significant risk factor for atherosclerosis.
  • Matrix metalloproteinases (MMPs) play a role in extracellular matrix remodeling and are implicated in atherosclerosis.
  • Genetic variations in MMP genes may influence an individual's susceptibility to atherosclerosis.

Purpose of the Study:

  • To investigate the association between MMP-9 (rs17576, rs3918242) and MMP-3 (rs3025058) gene polymorphisms and carotid atherosclerosis markers in T2DM patients.
  • To determine the relationship between these MMP gene polymorphisms and subclinical coronary artery disease markers in the same T2DM cohort.

Main Methods:

  • A prospective study involving 595 T2DM patients and 200 controls.
  • Ultrasonographic assessment of subclinical carotid atherosclerosis.
  • Coronary computed tomography angiography (CCTA) in a subset of T2DM patients.
  • Genotyping of MMP-9 (rs17576, rs3918242) and MMP-3 (rs3025058) polymorphisms using real-time PCR.

Main Results:

  • An association was found between the MMP-3 rs3025058 polymorphism and carotid intima-media thickness (CIMT) at baseline.
  • The A- allele or A- genotypes of rs3025058 (MMP-3) were linked to increased CIMT progression over 3.8 years.
  • The rs3025058 polymorphism demonstrated an effect on subclinical coronary atherosclerosis markers, including coronary calcium score and stenosis severity.

Conclusions:

  • The MMP-3 rs3025058 polymorphism is associated with subclinical carotid and coronary atherosclerosis in T2DM patients.
  • MMP-3 rs3025058 influences the progression of CIMT in T2DM patients over a 3.8-year follow-up period.
Keywords:
Carotid atherosclerosiscross-sectional studygenetic polymorphismmatrix metalloproteinase-3 genematrix metalloproteinase-9 geners17576rs3025058rs3918242

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