Coronary artery disease-associated genetic variants and biomarkers of inflammation

PLoS One. 2017 Jul 7;12(7):e0180365. doi: 10.1371/journal.pone.0180365. eCollection 2017.

Abstract

Introduction: Genetic constitution and inflammation both contribute to development of coronary artery disease (CAD). Several CAD-associated single-nucleotide polymorphisms (SNPs) have recently been identified, but their functions are largely unknown. We investigated the associations between CAD-associated SNPs and five CAD-related inflammatory biomarkers.

Methods: We genotyped 45 CAD-associated SNPs in 701 stable CAD patients in whom levels of high-sensitivity C-reactive protein (hsRCP), interleukin-6, calprotectin, fibrinogen and complement component 3 levels had previously been measured. A genetic risk score was calculated to assess the combined risk associated with all the genetic variants. A multiple linear regression model was used to assess associations between the genetic risk score, single SNPs, and the five inflammatory biomarkers.

Results: The minor allele (G) (CAD risk allele) of rs2075650 (TOMM40/APOE) was associated with lower levels of high-sensitivity C-reactive protein (effect per risk allele: -0.37 mg/l [95%CI -0.56 to -0.18 mg/l]). The inflammatory markers tested showed no association with the remaining 44 SNPs or with the genetic risk score.

Conclusions: In stable CAD patients, the risk allele of a common CAD-associated marker at the TOMM40/APOE locus was associated with lower hsCRP levels. No other genetic variants or the combined effect of all variants were associated with the five inflammatory biomarkers.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles*
  • Apolipoproteins E / blood
  • Apolipoproteins E / genetics
  • Biomarkers / metabolism
  • C-Reactive Protein / genetics*
  • C-Reactive Protein / metabolism
  • Complement C3 / genetics
  • Complement C3 / metabolism
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnosis*
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / pathology
  • Cross-Sectional Studies
  • Female
  • Fibrinogen / genetics
  • Fibrinogen / metabolism
  • Gene Expression
  • Genetic Loci*
  • Humans
  • Inflammation
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Leukocyte L1 Antigen Complex / blood
  • Leukocyte L1 Antigen Complex / genetics
  • Male
  • Membrane Transport Proteins / blood
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Mitochondrial Precursor Protein Import Complex Proteins
  • Polymorphism, Single Nucleotide*
  • Risk Factors

Substances

  • Apolipoproteins E
  • Biomarkers
  • C3 protein, human
  • Complement C3
  • IL6 protein, human
  • Interleukin-6
  • Leukocyte L1 Antigen Complex
  • Membrane Transport Proteins
  • Mitochondrial Precursor Protein Import Complex Proteins
  • TOMM40 protein, human
  • Fibrinogen
  • C-Reactive Protein

Grants and funding

Funding was received from the Novo Nordic Foundation (grant no. NNF14OC0008817 to SDK) and Pfizer (unrestricted research grant no. WS2632086 to HKJ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.