Key result
In patients with coronary artery disease and metabolic syndrome, the MMP-9 -1562 T-allele was associated with a 5.5-fold increased risk of composite clinical events compared to the CC genotype.
Why the study?
Does the MMP-9 -1562 C/T polymorphism increase the risk of clinical events in CAD patients with metabolic syndrome?
Cohort (n=1,000)
Does the MMP-9 -1562 C/T polymorphism increase the risk of clinical events in CAD patients with metabolic syndrome?
Odds Ratio: 5.5 (95% CI 2.3–13.2)
p-value: p=<0.001
The MMP-9 -1562 T-allele significantly increases the risk of future clinical events in patients with coronary artery disease and metabolic syndrome, suggesting a synergistic gene-environment interaction.
Should not yet guide risk stratification or genotyping in CAD with metabolic syndrome; leaves open independent validation in prospective cohorts.
BACKGROUND AND OBJECTIVES: Elevated levels of matrix metalloproteinase (MMP)-9 have been associated with the metabolic syndrome (MetS) and cardiovascular events. The MMP-9 -1562 C/T polymorphism has furthermore been shown as a risk factor for coronary artery disease (CAD). The non-favourable cardiometabolic state in MetS may increase the risk. We aimed to investigate the influence of MMP-9 -1562 C/T polymorphism in subjects with CAD and MetS. METHODS: Patients (n = 1000) with verified CAD stratified in Mets +/- (n = 244/756), were analyzed for the MMP-9 -1562 C/T polymorphism and related to clinical events after 2 years follow-up. Serum levels of total MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1 were analyzed in all, whereas MMP-9 activity, extracellular matrix metalloproteinase inducer (EMMPRIN), and expression of the two genes were analyzed in a subset of 240 randomly selected patients. RESULTS: Totally, 106 clinical endpoints were recorded. In MetS; the T-allele associated with 5.5 fold increase in event rate (p<0.0001), increased with number of MetS components, a 117% increase in total MMP-9 levels (TT homozygous, p = 0.05), significantly higher total- and endogenous active MMP-9 and TIMP-1 levels (p<0.01 all), and EMMPRIN was inversely correlated with pro- and endogenous active MMP-9 (p<0.05, both). In non-MetS; the T-allele was not associated with new events, nor higher MMP-9 levels. EMMPRIN was significantly correlated with total MMP-9 and TIMP-1 (p<0.01, both) and the two genes were inter-correlated (p<0.001). CONCLUSION: In CAD patients with MetS, the MMP-9 T-allele increased the risk of clinical events, probably mediated through elevated MMP-9 levels and altered MMP-9 regulation.
No takes yet. Share an insight, caveat, or question.
Opstad et al. (2014) conducted a cohort in Coronary Artery Disease (n=1,000). MMP-9 -1562 T-allele vs. MMP-9 -1562 CC genotype was evaluated on Composite of nonfatal AMI, unstable angina pectoris, stroke and all-cause mortality (OR 5.5, 95% CI 2.3-13.2, p=<0.001). In patients with coronary artery disease and metabolic syndrome, the MMP-9 -1562 T-allele was associated with a 5.5-fold increased risk of composite clinical events compared to the CC genotype.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: