Association Study of Coronary Artery Disease-Associated Genome-Wide Significant SNPs with Coronary Stenosis in Pakistani Population

Dis Markers. 2020 Jun 27:2020:9738567. doi: 10.1155/2020/9738567. eCollection 2020.


Genome-wide association studies (GWAS) of coronary artery disease (CAD) have revealed multiple genetic risk loci. We assessed the association of 47 genome-wide significant single-nucleotide polymorphisms (SNPs) at 43 CAD loci with coronary stenosis in a Pakistani sample comprising 663 clinically ascertained and angiographically confirmed cases. Genotypes were determined using the iPLEX Gold technology. All statistical analyses were performed using R software. Linkage disequilibrium (LD) between significant SNPs was determined using SNAP web portal, and functional annotation of SNPs was performed using the RegulomeDB and Genotype-Tissue Expression (GTEx) databases. Genotyping comparison was made between cases with severe stenosis (≥70%) and mild/minimal stenosis (<30%). Five SNPs demonstrated significant associations: three with additive genetic models PLG/rs4252120 (p = 0.0078), KIAA1462/rs2505083 (p = 0.005), and SLC22A3/rs2048327 (p = 0.045) and two with recessive models SORT1/rs602633 (p = 0.005) and UBE2Z/rs46522 (p = 0.03). PLG/rs4252120 was in LD with two functional PLG variants (rs4252126 and rs4252135), each with a RegulomeDB score of 1f. Likewise, KIAA1462/rs2505083 was in LD with a functional SNP, KIAA1462/rs3739998, having a RegulomeDB score of 2b. In the GTEx database, KIAA1462/rs2505083, SLC22A3/rs2048327, SORT1/rs602633, and UBE2Z/rs46522 SNPs were found to be expression quantitative trait loci (eQTLs) in CAD-associated tissues. In conclusion, five genome-wide significant SNPs previously reported in European GWAS were replicated in the Pakistani sample. Further association studies on larger non-European populations are needed to understand the worldwide genetic architecture of CAD.

MeSH terms

  • Adult
  • Aged
  • Cell Adhesion Molecules / genetics
  • Coronary Artery Disease / genetics*
  • Coronary Stenosis / genetics*
  • Female
  • Genome-Wide Association Study
  • Humans
  • Male
  • Middle Aged
  • Organic Cation Transport Proteins / genetics
  • Pakistan
  • Polymorphism, Single Nucleotide*
  • Quantitative Trait Loci
  • Ubiquitin-Conjugating Enzymes / genetics
  • White People / genetics


  • Cell Adhesion Molecules
  • JCAD protein, human
  • Organic Cation Transport Proteins
  • solute carrier family 22 (organic cation transporter), member 3
  • UBE2Z protein, human
  • Ubiquitin-Conjugating Enzymes