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Published on: April 1, 2019

Coronary artery disease and the thrombospondin single nucleotide polymorphisms

Olga I Stenina1, Tatiana V Byzova, Josephine C Adams

  • 1Joseph J. Jacobs Center for Thrombosis and Vascular Biology and Department of Molecular Cardiology/NB50, Cleveland Clinic Foundation/Lerner Research Institute, 9500 Euclid Avenue, Cleveland, OH 44195, USA.

The International Journal of Biochemistry & Cell Biology
|April 20, 2004
PubMed

Insights

GeneQuest identified three thrombospondin gene family single nucleotide polymorphisms (SNPs) strongly linked to premature coronary artery disease. These SNPs significantly alter thrombospondin structure and function, potentially promoting atherosclerosis.

Area of Science:

  • Genetics and Cardiovascular Disease Research

Background:

  • Familial premature coronary artery disease (CAD) and myocardial infarction (MI) have complex genetic underpinnings.
  • High-throughput, large-scale genetic analyses are crucial for identifying disease-associated genes.

Purpose of the Study:

  • To identify specific genes associated with familial premature CAD and MI using the GeneQuest analysis.
  • To investigate the functional and structural impact of identified single nucleotide polymorphisms (SNPs) within the thrombospondin gene family.

Main Methods:

  • Conducted a high-throughput, large-scale analysis of single nucleotide polymorphisms (SNPs) in a cohort with familial premature CAD and MI.
  • Utilized predictive analyses and experimental evidence to assess the structural and functional consequences of identified SNPs in thrombospondin-1, -2, and -4.

Main Results:

  • Identified three significant SNPs within the thrombospondin gene family (thrombospondin-1, -2, and -4) associated with premature CAD and MI.
  • Determined that SNPs in thrombospondin-1 and -4 result in amino acid substitutions, while the thrombospondin-2 SNP is in the 3'-untranslated region.
  • Observed altered conformational stability in thrombospondin-1, predicted structural changes in thrombospondin-2 and -4, and functional differences in thrombospondin-4's support of endothelial cell adhesion and proliferation.

Conclusions:

  • The identified SNPs in thrombospondin genes show marked effects on protein structure and function.
  • These alterations are consistent with a proatherogenic and prothrombotic phenotype, suggesting a role in premature CAD and MI pathogenesis.
  • Further research is needed to fully elucidate the mechanisms by which these thrombospondin polymorphic forms influence coronary artery disease.

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