title: The co-existence of the IL-18+183 A/G and MMP-9 -1562 C/T polymorphisms is associated with clinical events in coronary artery disease patients.
abstract: OBJECTIVE
  Interleukin (IL)-18 has been associated with severity of atherosclerosis and discussed to predict cardiovascular (CV) events. We have previously shown that the IL-18+183 G-allele significantly reduces IL-18 levels. This study was aimed to investigate the prognostic significance of the IL-18+183 A/G polymorphism (rs5744292), single and in coexistence with the matrix metalloproteinase (MMP)-9 -1562 C/T (rs3918242) polymorphism, in patients with stable coronary artery disease (CAD). Serum levels of IL-18, MMP-9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 were additionally assessed.
  
  
  METHODS
  1001 patients with angiographically verified CAD were genotyped and the biomarkers were measured accordingly. After two years follow-up, 10.6% experienced new clinical events; acute myocardial infarction (AMI), stroke, unstable angina pectoris and death.
  
  
  RESULTS
  The IL-18+183 G-allele associated with 35% risk reduction in composite endpoints after adjusting for potential covariates (p = 0.044). The IL-18+183 AA/MMP-9 -1562 CT/TT combined genotypes associated with a significant increase in risk of composite endpoints (OR = 1.87; 95% CI = 1.13-3.11, p = 0.015, adjusted). Patients with clinical events presented with significantly higher IL-18 levels as compared to patients without (p = 0.011, adjusted). The upper tertile of IL-18 levels associated with an increase in risk of AMI as compared to lower tertiles (OR = 2.36; 95% CI = 1.20-4.64, p = 0.013, adjusted).
  
  
  CONCLUSIONS
  The IL-18+183 A/G polymorphism, single and in combination with MMP-9 genotypes, may influence the risk of clinical events in stable CAD patients.
authors.affiliation: Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway ; Center for Heart Failure Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Trine B
authors.initials: TB
authors.lastname: Opstad
authors.forename: Alf Å
authors.initials: AÅ
authors.lastname: Pettersen
authors.forename: Harald
authors.initials: H
authors.lastname: Arnesen
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Seljeflot
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000789:Angina, Unstable / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D003324:Coronary Artery Disease / Q000150:complications / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D005787:Gene Frequency; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016019:Survival Analysis
chemical_list: D020382:Interleukin-18; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
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