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

• Published in: PloS one 2013-09, Vol.8 (9), p.e74498-e74498
• Main Authors: Opstad, Trine B, Pettersen, Alf Å, Arnesen, Harald, Seljeflot, Ingebjørg
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Alleles; Angina; Angina pectoris; Angina, Unstable - etiology; Angina, Unstable - genetics; Angina, Unstable - mortality; Angina, Unstable - pathology; Arteriosclerosis; Aspirin; Atherosclerosis; Biomarkers; Cardiology; Cardiovascular disease; Cell adhesion & migration; Cerebral infarction; Coexistence; Coronary artery; Coronary artery disease; Coronary Artery Disease - complications; Coronary Artery Disease - genetics; Coronary Artery Disease - mortality; Coronary Artery Disease - pathology; Coronary heart disease; Coronary vessels; Cytokines; Diabetes; Female; Follow-Up Studies; Gelatinase B; Gene Frequency; Gene polymorphism; Genetic aspects; Genotypes; Haplotypes; Health risk assessment; Heart attacks; Heart diseases; Heart failure; Hospitals; Humans; Interleukin; Interleukin 18; Interleukin-18 - genetics; Laboratories; Male; Matrix metalloproteinase; Matrix Metalloproteinase 9 - genetics; Metabolic syndrome; Metalloproteinase; Middle Aged; Mortality; Myocardial infarction; Myocardial Infarction - etiology; Myocardial Infarction - genetics; Myocardial Infarction - mortality; Myocardial Infarction - pathology; Patients; Polymorphism; Polymorphism, Single Nucleotide; Risk; Risk Factors; Serum levels; Studies; Survival Analysis; Tissue inhibitor of metalloproteinases; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0074498

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. 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. 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). 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.