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

Cheema A. N., PİRİM D., Wang X., Ali J., Bhatti A., John P., ...Daha Fazla

DISEASE MARKERS, cilt.2020, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 2020
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1155/2020/9738567
  • Dergi Adı: DISEASE MARKERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Agricultural & Environmental Science Database, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, EMBASE, MEDLINE, Directory of Open Access Journals
  • Bursa Uludağ Üniversitesi Adresli: Evet

Özet

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 modelsPLG/rs4252120 (p=0.0078),KIAA1462/rs2505083 (p=0.005), andSLC22A3/rs2048327 (p=0.045) and two with recessive modelsSORT1/rs602633 (p=0.005) andUBE2Z/rs46522 (p=0.03).PLG/rs4252120 was in LD with two functionalPLGvariants (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, andUBE2Z/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.