Licia Iacoviello, MD, PhD, Laboratory of Genetic and Environmental Epidemiology, Research Laboratories, Fondazione di Ricerca e Cura "Giovanni Paolo II", Catholic University, Largo Gemelli 1, 86100 Campobasso, Italy, Tel.: +39 0874 312274, Fax: +39 0874 312710, E-mail: .
[Show abstract][Hide abstract] ABSTRACT: Objective
To assess the influence of pro-inflammatory IL-1 genotype status on the risk of CAD, defined as >50% diameter stenosis, and cardiovascular events mediated by OxPL and Lp(a).
Oxidized phospholipids (OxPL) are pro-inflammatory, circulate on lipoprotein (a) [Lp(a)] and mediate coronary artery disease (CAD). Genetic variations in the interleukin-1 (IL-1) region are associated with increased inflammatory mediators.
IL-1 genotypes, OxPL on apolipoprotein B-100 (OxPL/apoB) and Lp(a) levels were measured in 499 patients undergoing coronary angiography. The composite genotype termed IL-1(+) was defined by three single nucleotide polymorphisms (SNPs) in the IL-1 gene cluster associated with higher levels of pro-inflammatory cytokines. All other IL-1 genotypes were termed IL-1(-).
Among IL-1(+) patients, the highest quartile of OxPL/apoB was significantly associated with a higher risk of CAD compared to the lowest quartile (OR 2.84, P=0.001). This effect was accentuated in patients ≤60 years old (OR 7.03, P<0.001). In IL-1(-) patients, OxPL/apoB levels showed no association with CAD. The interaction was significant for OxPL/apoB (OR 1.99, P=0.004) and Lp(a) (OR 1.96, P<0.001) in IL-1(+) versus IL-1(-) groups for patients ≤60 years old but not for patients >60 years old. In IL-1(+) patients ≤60 years old, after adjusting for established risk factors, high sensitivity C-reactive protein and Lp(a), OxPL/apoB remained an independent predictor of CAD. IL-1(+) patients above the median OxPL/apoB presented to the cardiac catheterization laboratory a mean of 3.9 years earlier (P=0.002) and had worse 4-year event-free survival (death, MI, stroke, and revascularization) compared to other groups (P=0.006).
Our study suggests that IL-1 genotype status can stratify population risk for CAD and cardiovascular events mediated by OxPL. These data suggest a clinically-relevant biological link between pro-inflammatory IL-1 genotypes, oxidation of phospholipids, Lp(a) and genetic predisposition to CAD and cardiovascular events.
Journal of the American College of Cardiology 05/2014; 63(17). · 15.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Interleukin-6 (IL-6) plays a critical role in the development and progression of cardiovascular disease. Emerging evidence suggests that two common polymorphisms (-174 G/C and -572 G/C) in the IL-6 gene might have an impact on an individual's susceptibility to myocardial infarction (MI), but individually published results are inconclusive. This meta-analysis aimed to derive a more precise estimation of the relationship between IL-6 -174 G/C and -572 G/C polymorphisms and MI risk. Method: An extensive literary search for relevant studies was conducted in PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases from their inception through August 1st, 2013. A meta-analysis was then performed using the STATA 12.0 software. The crude odds ratios (OR) with 95% confidence intervals (CI) were calculated. Results: Eleven case-control studies were included with a total of 10,252 subjects, including 5429 MI patients and 4823 healthy controls. Our meta-analysis results indicated that IL-6 -174 G/C polymorphism may increase the risk of MI (C allele vs. G allele: OR=1.07, 95% CI: 1.01-1.14, p=0.018; GC+CC vs. GG: OR=1.14, 95% CI: 1.04-1.24, p=0.003; respectively). However, our results showed no significant association between IL-6 -572 G/C polymorphism and MI risk (C allele vs. G allele: OR=0.88, 95% CI: 0.75-1.03, p=0.098; GC+CC vs. GG: OR=0.87, 95% CI: 0.70-1.07, p=0.173; respectively). No publication bias was detected in this meta-analysis. Conclusion: The current meta-analysis suggests that IL-6 -174 G/C polymorphism may contribute to MI susceptibility. Thus, detection of IL-6 -174 G/C polymorphisms may be a promising biomarker for the early detection of MI. However, IL-6 -572 G/C polymorphism may not associate with the risk of MI.
Genetic Testing and Molecular Biomarkers 03/2014; · 1.44 Impact Factor
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