title: Common haplotype of interleukin-6 gene is associated with chronic total occlusions of coronary arteries.
abstract: OBJECTIVE
  Genetic polymorphisms in genes coding for cytokines may predispose patients to coronary artery disease and chronic total occlusion (CTO) of coronary arteries. The aim of the study was to evaluate association of common genetic variations of interleukins (IL) with CTOs.
  
  
  METHODS
  We reviewed coronary angiograms and evaluated presence of CTOs in 684 consecutive patients with no history of revascularization. The following genetic variations were analyzed: IL-1B +3954 C>T, IL-1B -511 C>T, IL-1RN VNTR and haplotypes of IL-6 encompassing IL-6 -596 G>A, IL-6 -572 G>C, IL-6 -373 AnTn and IL-6 -174 G>C polymorphisms.
  
  
  RESULTS
  In 254 patients (37.1%) CTO of at least one artery was found. We observed nine IL-6 haplotypes, of which five were common (>1%) and one (GG9/12G, n=8) was not previously reported in literature. The most prevalent IL-6 haplotype (AG8/12C or Hap*1, 49.5%) correlated with CTOs, that were present in 31.5%, 36.5% and 44.5% of patients with none, one and two Hap*1, respectively (OR [95%CI] 1.252 [0.844-1.856] and 1.746 [1.104-2.762] for heterozygots and homozygots, respectively). In multivariate analysis this association became non-significant (OR [95%CI] 1.202 [0.805-1.796] and 1.529 [0.955-2.450]). In subgroup analysis Hap*1 was, however, associated with CTOs in the left anterior descending artery (p for trend 0.032) and the left circumflex artery (P=0.047), but not in the right coronary artery (p=0.799). In multivariate analysis CTOs of the left coronary arteries were associated only with total cholesterol (OR [95%CI] 1.170 [1.020-1.341]) and Hap*1 (OR [95%CI] 1.469 [0.914-2.361] and 1.970 [1.151-3.372] for heterozyogots and homozygots, respectively).
  
  
  CONCLUSIONS
  Our study suggests that common IL-6 haplotype (AG8/12C or Hap*1) is associated with development of CTOs in left coronary arteries.
authors.affiliation: Latvian Center of Cardiology, Paul Stradins Clinical University Hospital, Riga, Latvia. gustavs.latkovskis@gmail.com
authors.forename: G
authors.initials: G
authors.lastname: Latkovskis
authors.forename: N
authors.initials: N
authors.lastname: Licis
authors.forename: M
authors.initials: M
authors.lastname: Zabunova
authors.forename: M
authors.initials: M
authors.lastname: Berzina
authors.forename: I
authors.initials: I
authors.lastname: Narbute
authors.forename: S
authors.initials: S
authors.lastname: Jegere
authors.forename: A
authors.initials: A
authors.lastname: Erglis
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D002784:Cholesterol / Q000097:blood; D002908:Chronic Disease; D017023:Coronary Angiography; D054059:Coronary Occlusion / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics* / Q000276:immunology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D007844:Latvia; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D015415:Biomarkers; C508600:IL6 protein, human; D015850:Interleukin-6; D002784:Cholesterol