Genome-wide association study validation identifies novel loci for atherosclerotic cardiovascular disease

J Thromb Haemost. 2012 Aug;10(8):1508-14. doi: 10.1111/j.1538-7836.2012.04815.x.

Abstract

Background: Genetic variants influencing lipid levels and risk of coronary artery disease (CAD) have been identified by recent genome-wide association studies (GWAS).

Objectives: To test the association of single nucleotide polymorphisms (SNPs) implicated in lipoprotein metabolism and CAD in GWAS with atherosclerotic cardiovascular disease (ASCVD, including ischemic stroke [IS] and myocardial infarction [MI] phenotypes).

Patients and methods: A two-stage genetic association study was conducted in the Chinese Hans population. Stage I included a cohort with 451 IS cases and 462 controls for association analysis using 92 SNPs. Stage II examined the associations of eight positive variants and five additional variants with IS, MI and ASCVD in a cohort with 779 IS cases and 836 controls and a cohort with 824 MI cases and 737 controls.

Results: The T allele of rs4731702 located near the KLF14 gene was associated with a decreased risk of MI with an odds ratio (OR) of 0.72 (P<3.85×10(-3)). The rs4731702-T allele was also associated with a decreased risk of ASCVD with an OR of 0.78 (Pmeta-analysis<5.43×10(-4)). In addition, we found that a missense variant of KLF14, rs111400400 (Ser58Pro), was associated with MI.

Conclusion: Genetic variants newly identified near/in the KLF14 gene were implicated in the aetiology of atherosclerotic-related phenotypes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Asian People / genetics
  • Atherosclerosis / blood
  • Atherosclerosis / ethnology
  • Atherosclerosis / genetics*
  • Biomarkers / blood
  • Brain Ischemia / ethnology
  • Brain Ischemia / genetics
  • Case-Control Studies
  • China / epidemiology
  • Female
  • Gene Frequency
  • Genetic Loci*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Kruppel-Like Transcription Factors
  • Lipids / blood
  • Logistic Models
  • Male
  • Middle Aged
  • Myocardial Infarction / ethnology
  • Myocardial Infarction / genetics
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Risk Assessment
  • Risk Factors
  • Sp Transcription Factors / genetics*
  • Stroke / ethnology
  • Stroke / genetics

Substances

  • Biomarkers
  • KLF14 protein, human
  • Kruppel-Like Transcription Factors
  • Lipids
  • Sp Transcription Factors