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A functionally significant polymorphism in ID3 is associated with human coronary pathology.

Ani Manichaikul1, Stephen S Rich2, Heather Perry3

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The ID3 SNP rs11574 risk allele is linked to coronary artery pathology, including coronary artery calcium and atheroma burden. This finding reinforces the association between this genetic marker and cardiovascular disease progression in diverse populations.

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Area of Science:

  • Genetics and Cardiovascular Disease Research
  • Molecular Biology and Atherosclerosis

Background:

  • Previous studies identified an association between the ID3 SNP rs11574 and carotid intima-media thickness in a diabetic population.
  • The rs11574 single nucleotide polymorphism (SNP) alters the ID3 protein, affecting its role in gene transcription.
  • This study investigates the link between this functional SNP and human coronary artery pathology.

Purpose of the Study:

  • To characterize the association between the ID3 gene polymorphism rs11574 and human coronary pathology.
  • To validate findings in a multi-ethnic cohort and a cohort undergoing cardiac catheterization.

Main Methods:

  • Analysis of the Multi-Ethnic Study of Atherosclerosis (MESA) cohort (n=7,178) including coronary artery calcium (CAC) data.
  • Evaluation of the Coronary Assessment in Virginia (CAVA) cohort (n=71) using intravascular ultrasound (IVUS) during cardiac catheterization.
  • Statistical analysis, including multivariate analysis, to assess the predictive value of the ID3 rs11574 risk allele.

Main Results:

  • The ID3 rs11574 risk allele was associated with the presence of CAC in White participants of the MESA study (P=0.017).
  • In the CAVA cohort, the risk allele correlated with increased atheroma burden and stenosis (P=0.003 and P=0.04, respectively).
  • The risk allele remained a significant predictor of atheroma burden in multivariate analyses, even after adjusting for clinical factors like hypertension and diabetes.

Conclusions:

  • The ID3 SNP rs11574 is directly associated with human coronary artery pathology, as evidenced by CAC and IVUS findings.
  • These results extend the observed association to multi-ethnic, relatively healthy populations and a predominantly White population with type 2 diabetes mellitus (T2DM).
  • The study confirms the role of ID3 rs11574 as a potential biomarker for coronary artery disease risk.