Abstract
BackgroundSeveral studies have evaluated the association between plasminogen activator inhibitor-1 (PAI-1) -675 4G/5G polymorphism and sepsis in different populations. However, the available results are conflicting.MethodsA search of Pubmed and EMBASE databases was performed to identify relevant studies for inclusion in the meta-analysis. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were determined using a random-effects model.ResultsTwelve case-control studies and three cohort studies were included. Overall, a significant association between 4G/5G polymorphism and sepsis risk was observed for 4G/4G vs. 4G/5G +5G/5G (OR = 1.30, 95% CI 1.08–1.56, P = 0.006). In addition, there was a significant association between PAI-1 4G/5G polymorphism and sepsis-related mortality (OR = 1.72, 95% CI 1.27–2.33, P = 0.0005). In subgroup analyses, increased sepsis risk and mortality risk were found in Caucasians and in patients with sepsis.ConclusionsThis meta-analysis suggested that the PAI-1 -675 4G/5G polymorphism was a risk factor for sepsis and sepsis mortality.
Highlights
Sepsis is a major public health problem that is responsible for an estimated economic burden of nearly 17 billion dollars annually in the United States
A number of investigators have begun the search for genetic risk factors that influence clinical outcomes in sepsis, and the plasminogen activator inhibitor-1 (PAI-1) gene has been studied extensively
In patients with meningococcal sepsis, previous studies showed that concentrations of PAI-1 were markedly elevated and there was a significant correlation between PAI-1 levels and mortality [5,6]
Summary
Sepsis is a major public health problem that is responsible for an estimated economic burden of nearly 17 billion dollars annually in the United States. A number of investigators have begun the search for genetic risk factors that influence clinical outcomes in sepsis, and the plasminogen activator inhibitor-1 (PAI-1) gene has been studied extensively. Zeerleder and coworkers reported that PAI-1 levels were significantly higher in septic shock patients than in severe sepsis patients [3]. In patients with meningococcal sepsis, previous studies showed that concentrations of PAI-1 were markedly elevated and there was a significant correlation between PAI-1 levels and mortality [5,6]. Taken together, these results suggest that PAI-1 may play a pivotal role in the pathogenesis of sepsis.
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