title: The -174 G>C Interleukin-6 Gene Polymorphism is Associated with Angiographic Progression of Coronary Artery Disease over a 4-Year Period.
abstract: BACKGROUND
  Inflammation is a key process underlying the clinical course of coronary artery disease (CAD). C-reactive protein (CRP) and interleukin-6 (IL-6) contribute to its pathophysiology and act as biomarkers. We sought to examine whether known single nucleotide polymorphisms (SNPs) impact CAD progression, reflecting increased inflammation.
  
  
  METHODS
  We retrospectively evaluated coronary angiographies of patients with established CAD who were re-investigated for stable/unstable angina after a time interval of >12 months. We defined progression of CAD as the emergence of a new plaque or a ≥20 % increase of a formerly non-significant lesion. We genotyped patients for the 1846 C>T CRP and -174 G>C IL-6 SNPs. The probability of CAD progression among the Mendelian randomization groups was evaluated using the Kaplan-Meier method. Data were analyzed using a Cox model that included relevant clinical factors.
  
  
  RESULTS
  A total of 157 patients were included. The serum levels of CRP and IL-6 differed significantly between genotypes. The genotype frequencies of IL-6 were consistent with Hardy-Weinberg equilibrium, whereas those for CRP were excluded from our conclusions. At 48 months, 83 patients (52.9 %) with the IL-6 C allele versus 74 (47.1 %) with the G allele exhibited CAD progression. Patients with the IL-6 C allele had a 52.8 % probability for progression versus 13.3 % for those with the G allele (p=0.005). The results were confirmed by multivariate analysis; dyslipidemia, family history, and IL-6 SNP emerged as significant factors.
  
  
  CONCLUSIONS
  Patients with established CAD who carried the -174 C allele of the IL-6 gene demonstrated an increased risk for the progression of coronary plaques over a four-year period. Further studies will be needed to validate these findings.
authors.affiliation: First Department of Cardiology, Athens Medical School, Hippokration General Hospital, Greece. Electronic address: ktoutouz@gmail.com.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Toutouzas
authors.affiliation: First Department of Cardiology, Athens Medical School, Hippokration General Hospital, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Klettas
authors.affiliation: First Department of Cardiology, Athens Medical School, Hippokration General Hospital, Greece.
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Anousakis-Vlachochristou
authors.affiliation: First Department of Cardiology, Athens Medical School, Hippokration General Hospital, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Melidis
authors.affiliation: First Department of Cardiology, Athens Medical School, Hippokration General Hospital, Greece.
authors.forename: Zeta
authors.initials: Z
authors.lastname: Azilazian
authors.affiliation: First Department of Cardiology, Athens Medical School, Hippokration General Hospital, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Asimomiti
authors.affiliation: First Department of Cardiology, Athens Medical School, Hippokration General Hospital, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Karanasos
authors.affiliation: Naval Hospital of Athens, Greece.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Spanos
authors.affiliation: First Department of Cardiology, Athens Medical School, Hippokration General Hospital, Greece.
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Tsiamis
authors.affiliation: First Department of Cardiology, Athens Medical School, Hippokration General Hospital, Greece.
authors.forename: Petros
authors.initials: P
authors.lastname: Nihoyannopoulos
authors.affiliation: First Department of Cardiology, Athens Medical School, Hippokration General Hospital, Greece.
authors.forename: Dimitris
authors.initials: D
authors.lastname: Tousoulis
mesh_terms: D000368:Aged; D000483:Alleles; D000789:Angina, Unstable / Q000000981:diagnostic imaging*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D017023:Coronary Angiography / Q000379:methods*; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D002097:C-Reactive Protein
keywords: Coronary artery disease; SNP; gene polymorphisms; inflammation; interleukin-6; progression