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